ncRNA_name ncRNAID ncRNA type Subcellular location Species Diseases Cell lines/Tissue Techniques Used reagents target Ferroptosis pathway/component Regulation Description Title Year PMID circRNA1615 - circRNA - mouse Myocardial Infarction cardiomyocytes Luciferase Reporter Experiments erastin miRNA152-3p/LRP6 GPX4 circRNA1615 inhibits ferroptosis circRNA1615 inhibited ferroptosis in cardiomyocytes, and circRNA1615 could regulate the expression of LRP6 through sponge adsorption of miR-152-3p, prevent LRP6-mediated autophagy-related ferroptosis in cardiomyocytes, and finally control the pathological process of MI. Effect and Mechanism of LRP6 on Cardiac Myocyte Ferroptosis in Myocardial Infarction 2021 34712388 circGFRA1 - circRNA - H.sapiens Breast Cancer breast cancer tissues Western blotting - miR-1228-AIFM2 GPX4 knockdown of circGFRA1 promotes ferroptosis Combined with the confirmation that the decrease in the GSH/GSSG ratio results in the deactivation of GPX4, which in turn leads to more toxic lipid reactive oxygen species (ROS) accumulation and ferroptosis induction, we can deduce that knockdown of circGFRA1 promotes ferroptosis. In addition, it has been proven that the two pathways mentioned above act in parallel with each other. CircGFRA1 facilitates the malignant progression of HER-2-positive breast cancer via acting as a sponge of miR-1228 and enhancing AIFM2 expression 2021 34668628 circDTL - circRNA cytoplasm/Nuclear H.sapiens Non-Small Cell Lung Cancer lung epithelial cell line BEAS-2B and human NSCLC cell lines CCK-8 assay erastin miR-1287-5p/GPX4 lipid ROS silencing of circDTL induced ferroptosis This study found that circDTL was upregulated and acted as an oncogene during the progression of NSCLC. Interestingly, silencing of circDTL induced ferroptosis of NSCLC cells and further investigation showed that circDTL regulated ferroptosis via the miR-1287-5p/GPX4 axis. These findings underlined the importance of circRNAs in the process of ferroptosis and introduced circDTL as a regulator of ferroptosis in NSCLC. CircDTL Functions as an Oncogene and Regulates Both Apoptosis and Ferroptosis in Non-small Cell Lung Cancer Cells 2021 34621297 circRHBG - circRNA - H.sapiens Polycystic Ovary Syndrome KGN and SVOG cells CCK-8 assay - miR515-5p/SLC7A11 glutathione circRHBG knockdown promotes ferroptosis CircRNA high-throughput chips and qRT-PCR verified that circRHBG was significantly upregulated in granular cells of PCOS patients. Knockdown of circRHBG inhibits KGN and SVOG cell proliferation. Luciferase reporter assays and Ago2-RIP detection showed that circRHBG competes with SLC7A11 to bind to miR-515-5p. Subsequent experiments verified knockdown of circRHBG promotes ferroptosis in PCOS. Involvement of ferroptosis in the granulosa cells proliferation of PCOS through the circRHBG/miR-515/SLC7A11 axis 2021 34532485 circFNDC3B - circRNA - H.sapiens Oral Squamous Cell Carcinoma CAL27 and SCC15 cell lines CCK-8 assay erastin miR-520d-5p/SLC7A11 lipid ROS circFNDC3B attenuated ferroptosis Our data demonstrated that the silencing of circFNDC3B by shRNA inhibited GPX4 and SLC7A11 expression and enhanced ROS, iron, and Fe2+ levels in OSCC cells. CircFNDC3B knockdown reinforced erastin-induced inhibitory effect on OSCC cells. The depletion of circFNDC3B repressed cell proliferation and enhanced cell apoptosis of OSCC cells. Circular RNA FNDC3B Protects Oral Squamous Cell Carcinoma Cells From Ferroptosis and Contributes to the Malignant Progression by Regulating miR-520d-5p/SLC7A11 Axis 2021 34434890 circ_0067934 - circRNA - H.sapiens Thyroid Cancer FTC133 and TPC-1 cells DCFH-DA staining - miR-545-3p/SLC7A11 lipid ROS Circ_0067934 attenuated ferroptosis The knockdown of circ_0067934 induced thyroid cancer cell apoptosis and repressed thyroid cancer cell proliferation in vitro and in vivo. Circ_0067934 upregulated the expression of the ferroptosis-negative regulator SLC7A11 by sponging and inhibiting miR-545-3p in thyroid cancer cells. The overexpression of SLC7A11 or the inhibitor of miR-545-3p reversed circ_0067934 silencing-regulated thyroid cancer cell proliferation. Circular RNA Circ_0067934 Attenuates Ferroptosis of Thyroid Cancer Cells by miR-545-3p/SLC7A11 Signaling 2021 34290668 circKIF4A - circRNA - H.sapiens Thyroid Cancer thyroid tissues and primary papillary thyroid cancer samples - - miR-1231/GPX4 GPX4 circKIF4A facilitated the malignant progress We explored circKIF4A and the result showed that it had high expression in papillary thyroid cancer. The functions of circKIF4A were explored by CCK-8, transwell, and mouse xenograft experiments. Knockdown of circKIF4A could suppress papillary thyroid cell growth and migration. In addition, RIP assays and dual luciferase vector reporter assays were further conducted. Our consequence showed circKIF4A facilitated the malignant progress of papillary thyroid tumor by sponging miR-1231 and upregulating GPX4 expression. In conclusion, our study proved that circKIF4A-miR-1231-GPX4 axis played a vital role in cancer proliferation and ferroptosis by competing endogenous RNAs. Circular RNA circKIF4A facilitates the malignant progression and suppresses ferroptosis by sponging miR-1231 and upregulating GPX4 in papillary thyroid cancer 2021 34153004 circ0097009 - circRNA - H.sapiens Hepatocellular Cancer LO2 and HCC cell lines HepG2, BEL-7402, and MHCC-97H Glutathione - miR-1261/SLC7A11 GPX4 knockdown of circ0097009 promotes ferroptosis Microarray analysis and qRT-PCR verified that circRNA, circ0097009, was significantly upregulated in HCC tissues and cell lines. Knockdown of circ0097009 inhibited the proliferation and invasion of HCC cells. Luciferase reporter assays showed that circ0097009 and SLC7A11 directly bound to miR-1261. Subsequent experiments showed that circ0097009 and SLC7A11 reciprocally regulated their expression via miR-1261 sponging by circ0097009. Ferroptosis is involved in the progression of hepatocellular carcinoma through the circ0097009/miR-1261/SLC7A11 axis 2021 33987373 circSnx12 - circRNA - mice Heart Failure Cardiac tissues - - miR-224-5p FTH1 circSnx12 Is Involved in Ferroptosis we assessed the binding relationship between the ferroptosis-associated gene FTH1 and its target miR-224-5p. The results of luciferase reporter assay showed that miR-224-5p mimics could reduce the luciferase activity of FTH1 3'-UTR, but did not significantly affected that of FTH1 3'-UTR mutant. These findings imply that FTH1 is a direct target of miR-224-5p. Additionally, we demonstrated the regulatory relationship between miR-224-5p and circSnx12. circSnx12 Is Involved in Ferroptosis During Heart Failure by Targeting miR-224-5p 2021 33969020 circ_0007142 - circRNA cytoplasm H.sapiens Colorectal Cancer Cells HCT116, SW620 and SW480 CCK-8 assay - miR-874-3p/GDPD5 - Low circ_0007142 expression accelerate of apoptosis circ_0007142 was found as a miR-874-3p sponge and miR-874-3p inhibitor eliminated the regulation of si-circ_0007142 in CRC cells. MiR-874-3p targeted GDPD5 and upregulation of GDPD5 reversed the miR-874-3p-triggered tumour inhibition and ferroptosis promotion in CRC cells. Moreover, GDPD5 was regulated by the circ_0007142/miR-874-3p axis. Circ_0007142 also affected CRC tumorigenesis in vivo through the regulation of miR-874-3p and GDPD5. Circ_0007142 downregulates miR-874-3p-mediated GDPD5 on colorectal cancer cells 2021 33797091 circRHOT1 - circRNA - H.sapiens Breast Cancer MDA-MB-231 and T47D MTT assays - miR-106a-5p/STAT3 STAT3 CircRHOT1 inhibits ferroptosis the depletion of circRHOT1 enhanced the erastin-induced inhibition effect on cell growth of breast cancer cells. The circRHOT1 knockdown notably increased the levels of reactive oxygen species (ROS), iron, and Fe2+ in breast cancer cells. Mechanically, circRHOT1 was able to sponge microRNA-106a-5p (miR-106a-5p) and inhibited ferroptosis by down-regulating miR-106a-5p in breast cancer cells. Besides, miR-106a-5p induced ferroptosis by targeting signal transducer and activator of transcription 3 (STAT3) in the system. Moreover, the overexpression of STAT3 and miR-106a-5p inhibitor could reverse circRHOT1 knockdown-mediated breast cancer progression. Circular RNA RHOT1 promotes progression and inhibits ferroptosis via mir-106a-5p/STAT3 axis in breast cancer 2021 33686957 circEPSTI1 - circRNA - H.sapiens Cervical Cancer CaSki, HeLa, and HcerEpic Liperfluo staining and confocal microscopy - miR-375/409-3P/515-5p-SLC7A11 GPX4 Silencing of circEPSTI1 induces ferroptosis circEPSTI1 (hsa_circRNA_000479) was significantly upregulated in cervical cancer. We first discovered the impact of circRNA on cell ferroptosis in cervical cancer. Interestingly, circEPSTI1 attenuates the effect of ferritin which is mediated by SLC7A11 based on lipid peroxidation measurements and reduced glutathione and glutathione (GSH/GSSG) assay. Circular RNA circEPSTI1 accelerates cervical cancer progression via miR-375/409-3P/515-5p-SLC7A11 axis 2021 33534779 circIL4R - circRNA - H.sapiens Hepatocellular Carcinoma THLE-2 and HuH-7 MTT assays erastin miR-541-3p/GPX4 ROS CircIL4R knockdown impeded oncogenesis and expedited ferroptosis CircIL4R was abnormally overexpressed in HCC tissues and cells. CircIL4R knockdown impeded oncogenesis and expedited ferroptosis of HCC cells. CircIL4R could directly sponge microRNA-541-3p (miR-541-3p) and miR-541-3p inhibition mitigated the effects of circIL4R knockdown on HCC cells. CircIL4R acted as a miR-541-3p sponge to regulate its target glutathione peroxidase 4 (GPX4). GPX4 upregulation relieved the miR-541-3p-induced tumor inhibition and ferroptosis aggravation. CircIL4R played an oncogenic role in HCC via the miR-541-3p/GPX4 axis in vivo. CircIL4R facilitates the tumorigenesis and inhibits ferroptosis in hepatocellular carcinoma by regulating the miR-541-3p/GPX4 axis 2020 32808701 cIARS hsa_circ_0008367 circRNA - H.sapiens Hepatocellular Carcinoma HepG2, SMMC-7721, and Huh7 CCK-8 assay SF or Erastin ALKBH5 GSH cIARS to be a positive regulator of ferroptosis Prediction analysis and mechanistic identification revealed that cIARS physically interacted with RNA binding protein (RBP) ALKBH5, which was a negative regulator of autophagic flux in HCC. The dissociation of BCL-2/BECN1 complex, mediated by ALKBH5 silencing was effectively blocked by si-cIARS. Furthermore, the inhibition of ferroptotic events, autophagic flux and ferritinophagy resulted from si-cIARS, were significantly rescued by ALKBH5 downregulation. Circular RNA cIARS regulates ferroptosis in HCC cells through interacting with RNA binding protein ALKBH5 2020 32802409 circABCB10 - circRNA - H.sapiens Rectal Cancer SW837 and HR-8348 cell lines (up regulation) CCK-8 assay, C11-BODIPY staining, flow cytometry, iron assay Erastin miR-326 / CCL5 (C-C motif chemokine ligand 5) lipid ROS circABCB10 deletion-induced cell ferroptosis and apoptosis CircABCB10 performed carcinogenic functions to suppress ferroptosis and apoptosis in rectal cancer by regulating miR-326/CCL5 axis. CircABCB10 silencing inhibits the cell ferroptosis and apoptosis by regulating the miR-326/CCL5 axis in rectal cancer 2020 32567935 circ-TTBK2 - circRNA - H.sapiens Glioma LN229 and U251 cell lines (up regulation) iron assay, lipid ROS assay, MTT assay Erastin, Ferrostatin-1 miR-761 / ITGB8 lipid ROS Circ-TTBK2 regulated cell proliferation, invasion and ferroptosis Levels of circ-TTBK2 and ITGB8 were upregulated, whereas miR-761 level was low-expressed in glioma tissues and cells. CircTTBK2 was a sponge of miR-761 to modulate ITGB8. Additionally, circ-TTBK2 knockdown or miR-761 increase could retard cell proliferation, invasion, and promote ferroptosis in glioma cells. Interestingly, miR-761 inhibitor could abolish the repressive impact of circ-TTBK2 silencing on cell growth in vitro. Also, the influence of miR-761 mimic on cell phenotypes was regained after ITGB8 upregulation. Meanwhile, circ-TTBK2 deficiency caused the decrease of tumor growth. Circ-TTBK2 regulated cell proliferation, invasion and ferroptosis via targeting ITGB8 by sponging miR-761 in glioma, providing a promising biomarker for the clinical therapy of human glioma. 2020 32196629 RP11-89 ENSG00000259439 lncRNA - H.sapiens Bladder Cancer 5637 Cell and T24 Cell CCK-8 assay, flow cytometry, Transwell assays, scratch tests and subcutaneous nude mouse models - TMEM161B-AS1-hsa-miR-27a-3p-FANCD2/CD44 iron export positive We demonstrated that RP11-89 is a novel tumorigenic regulator that inhibits ferroptosis via PROM2-activated iron export. LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer 2021 34728613 TMEM161B-AS1 ENSG00000247828 lncRNA - H.sapiens Glioma U87 cells and U251 cells qRT-PCR,Cell transfection,Dual luciferase reporter assay,Tumor xenograft assay,CCK-8 assay - TMEM161B-AS1-hsa-miR-27a-3p-FANCD2/CD44 lipid ROS negative Knockdown of TMEM161B-AS1 down-regulated the expression of FANCD2 and CD44 by sponging hsa-miR-27a-3p, inhibited the proliferation, migration, invasion and promoted apoptosis, ferroptosis of U87 cells and U251 cells. Over-expression of lncRNA TMEM161B-AS1 promotes the malignant biological behavior of glioma cells and the resistance to temozolomide via up-regulating the expression of multiple ferroptosis-related genes by sponging hsa-miR-27a-3p 2021 34689169 ZFAS1 ENSG00000177410 lncRNA - H.sapiens Diabetic Cardiomyopathy cardiomyocytes Masson staining, immunohistochemical staining, Western blotting, monobromobimane staining, immunofluorescence staining and JC-1 staining - miR-150-5p/CCND2 GPX4 positive Inhibition of ZFAS1 led to reduced collagen deposition, decreased cardiomyocyte apoptosis and ferroptosis, and attenuated DbCM progression. ZFAS1 sponges miR-150-5p to downregulate CCND2 expression. Inhibition of the long non-coding RNA ZFAS1 attenuates ferroptosis by sponging miR-150-5p and activates CCND2 against diabetic cardiomyopathy 2021 34609043 Meg3 ENSMUSG00000021268 lncRNA - Rat Diabetic Brain Ischemic Injury microvascular endothelial cells Cell transfection,RT-PCR,Iron concentration assay,lipid ROS assay, - p53/GPX4 GPX4 positive Altogether, these data revealed that, by modulating GPX4 transcription and expression, the Meg3-p53 signaling pathway mediated the ferroptosis of RBMVECs upon injury induced by OGD combined with hyperglycemic reperfusion. Long noncoding RNA Meg3 mediates ferroptosis induced by oxygen and glucose deprivation combined with hyperglycemia in rat brain microvascular endothelial cells, through modulating the p53/GPX4 axis 2021 34587716 PVT1 ENSG00000249859 lncRNA cytoplasm H.sapiens Liver Cancer HepG2 and Huh7 CCK-8 assay ketamine, Erastin, or RSL3 miR-214-3p/GPX4 lipid ROS Ferroptosis Induced by siPVT1 LncPVT1 directly interacted with miR-214-3p to impede its role as a sponge of GPX4. Depletion of lncPVT1 accelerated the ferroptosis of live cancer cells, whereas miR-214-3p inhibition and GPX4 overexpression reversed this effect. Ketamine-induced cell growth suppression and ferroptosis were also suppressed by miR-214-3p inhibition and GPX4 overexpression. Ketamine Induces Ferroptosis of Liver Cancer Cells by Targeting lncRNA PVT1/miR-214-3p/GPX4 2021 34566408 H19 ENSG00000130600 lncRNA cytoplasm H.sapiens Intracerebral Hemorrhage Brain microvascular endothelial cells CCK-8 assay erastin miR-106b-5p GSH Knockdown of H19 promoted cell proliferation and suppressed BMVECs ferroptosis Over-expression of H19 suppressed cell viability and promoted ferroptosis of BMVECs. miR-106b-5p is predicted to be a target of H19. The expression of miR-106b-5p was lower in oxygen and glucose deprivation hemin-treated (OGD/H-treated) cells. Over-expression of miR-106b-5p reversed the effects of H19 on cell viability and ferroptosis in BMVECs. Furthermore, acyl-CoA synthetase long-chain family member 4 (ACSL4) was verified to be a target gene of miR-106b-5p and was highly expressed in OGD/H-treated cells. Upregulation of ACSL4 inhibited the effects of miR-106b-5p and induced BMVEC dysfunction. Long non-coding RNA H19 protects against intracerebral hemorrhage injuries via regulating microRNA-106b-5p/acyl-CoA synthetase long chain family member 4 axis 2021 34288826 OIP5-AS1 ENSG00000247556 lncRNA - H.sapiens Prostate Cancer PC3 and DU145 MTT assay Erastin and ferrostatin-1 miR-128-3p/SLC7A11 GSH OIP5-AS1 promotes PCa progression and ferroptosis resistance We found that lncRNA OIP5-AS1 expression was greatly elevated in PC3 and DU145 cells upon chronic Cd exposure. Dysregulation of OIP5-AS1 expression mediated cell growth and Cd-induced ferroptosis. Mechanistically, we demonstrated that OIP5-AS1 served as an endogenous sponge of miR-128-3p to regulate the expression of SLC7A11, a surrogate marker of ferroptosis. Moreover, miR-128-3p decreased cell viability by enhancing ferroptosis. LncRNA OIP5-AS1 inhibits ferroptosis in prostate cancer with long-term cadmium exposure through miR-128-3p/SLC7A11 signaling 2021 34051661 HOTAIR ENSG00000228630 lncRNA cytoplasm mice Intracerebral Haemorrhage HT22 MTT Assay - UPF1/ACSL4 ROS HOTAIR overexpression reversed paeonol-induced inhibition of ferroptosis Moreover, paeonol notably inhibited ferroptosis in hemin-treated neuronal cells via inhibition of ACSL4. Additionally, HOTAIR bound to UPF1, and UPF1 promoted the degradation of ACSL4 by binding to ACSL4. Furthermore, HOTAIR overexpression reversed paeonol-induced inhibition of ferroptosis by mediating the UPF1/ACSL4 axis. Paeonol inhibits the progression of ICH by mediating the HOTAIR/UPF1/ACSL4 axis. Paeonol inhibits the progression of intracerebral haemorrhage by mediating the HOTAIR/UPF1/ACSL4 axis 2021 33906483 MEG8 ENSG00000225746 lncRNA - H.sapiens Hemangioma hemangioma endothelial cells - Ferrostatin-1 miR-497-5p/NOTCH2 GPX4 knockdown of MEG8 inhibited the proliferation and induced the ferroptosis Knockdown of MEG8 increased the miR-497-5p expression and reduced the mRNA and protein levels of NOTCH2. Using a dual-luciferase assay, we confirmed the binding between MEG8 and miR-497-5p, and between the miR-497-5p and 3'UTR of NOTCH2. We further found that silencing MEG8 significantly decreased the expressions of SLC7A11 and GPX4 both in mRNA and protein level and had no effect on the level of AIFM2. Importantly, blocking miR-497-5p abrogated the effects of MEG8 loss on cell viability, MDA level and expression levels of NOTCH2, SLC7A11 and GPX4 in HemECs. Taken together, our results suggested that knockdown of long non-coding RNA MEG8 inhibited the proliferation and induced the ferroptosis of hemangioma endothelial cells by regulating miR-497-5p/NOTCH2 axis. Silencing long non-coding RNA MEG8 inhibits the proliferation and induces the ferroptosis of hemangioma endothelial cells by regulating miR-497-5p/NOTCH2 axis 2021 33839417 NEAT1 ENSG00000245532 lncRNA - H.sapiens Hbe And Nsclc non-small-cell lung cancer CCK8 assay erastin ACSL4 GPX4 NEAT1 regulates ferroptosis and ferroptosis sensitivity Erastin-induced cell death was positively correlated with ACSL4 level. NEAT1 regulated levels of ACSL4 and proteins related to the ferroptosis and classical apoptosis pathways. Levels of ACSL4, SLC7A11, and GPX4 were decreased more by NEAT1 silencing plus erastin than by erastin alone. Long non-coding RNA NEAT1 regulates ferroptosis sensitivity in non-small-cell lung cancer 2021 33730930 H19 ENSG00000130600 lncRNA cytoplasm H.sapiens Spontaneous Abortio placental villi tissues - Ferrostatin-1 Bcl-2 and GPX4 GPX4 H19 promoting apoptosis and ferroptosis H19 expression was positively correlated with Bcl-2 and GPX4 expression and negatively linked with Bax levels. It was demonstrated that silencing H19 downregulated Bcl-2 and GPX4 expression and upregulated Bax expression at both the mRNA and protein levels in HTR-8/SVneo trophoblast cells. In conclusion, the present findings suggested that H19 has important roles in SA by promoting apoptosis and ferroptosis. Long non-coding RNA H19 regulates Bcl-2, Bax and phospholipid hydroperoxide glutathione peroxidase expression in spontaneous abortion 2021 33273971 LINC00618 - lncRNA nucleus H.sapiens Leukemia HL60 and K562 Iron Assay Kit erastin BAX Lipid ROS LINC00618 accelerates ferroptosis LINC00618 promotes apoptosis by increasing the levels of BCL2-Associated X (BAX) and cleavage of caspase-3. LINC00618 also accelerates ferroptosis by increasing the levels of lipid reactive oxygen species (ROS) and iron, two surrogate markers of ferroptosis, and decreasing the expression of solute carrier family 7 member 11 (SLC7A11). Interestingly, VCR-induced ferroptosis and apoptosis are promoted by LINC00618, and LINC00618 accelerates ferroptosis in a manner dependent upon apoptosis. LINC00618 attenuates the expression of lymphoid-specific helicase (LSH), and LSH enhances the transcription of SLC7A11 after the recruitment to the promoter regions of SLC7A11, further inhibiting ferroptosis. A Nuclear Long Non-Coding RNA LINC00618 Accelerates Ferroptosis in a Manner Dependent upon Apoptosis 2021 33002417 MT1DP ENSG00000205361 lncRNA - H.sapiens Non-Small Cell Lung Cancer A549 and H1299 GSH assay kit erastin miR-365a-3p/NRF2 ROS MT1DP attenuated expression of NRF2 and increased sensitivity of NRF2-overexpressed non-small cell lung cancer (NSCLC) cells to erastin-induced ferroptosis In vivo analysis showed that E/M@FA-LPs had a favorable therapeutic effect on lung cancer xenografts. In short, our findings identify a novel strategy to elevate erastin-induced ferroptosis in NSCLCs acting through the MT1DP/miR-365a-3p/NRF2 axis. MT1DP loaded by folate-modified liposomes sensitizes erastin-induced ferroptosis via regulating miR-365a-3p/NRF2 axis in non-small cell lung cancer cells 2020 32929075 PVT1 ENSG00000249859 lncRNA cytoplasm H.sapiens Acute Ischemic Stroke plasma GSH/GSSG - miR-214/p53 GPX4 PVT1 regulated ferroptosis We found that the levels of PVT1 were upregulated and miR-214 levels were downregulated in plasma of AIS patients. NIHSS score was positively correlated with PVT1 levels but was negatively with miR-214 levels. PVT1 silencing or miR-214 overexpression significantly reduced infarct size and suppressed ferroptosis in vivo. miR-214 overexpression markedly decreased PVT1 levels. Specifically, miR-214 could bind to 3'untranslated region (3'UTR) of PVT1, TP53 or TFR1. PVT1 overexpression or miR-214 silencing markedly abolished the effects of Ferrostatin-1 on ferroptosis indicators except for TFR1 expression. Besides, miR-214 silencing counteracted the effects of PVT1 knockdown on the ferroptosis-related proteins. LncRNA PVT1 regulates ferroptosis through miR-214-mediated TFR1 and p53 2020 32827544 ZFAS1 ENSG00000177410 lncRNA cytoplasm H.sapiens Pulmonary Fibrosis HFL1 cell line (up regulation) lipid ROS assay, MDA assay, western blot Ferrostatin-1 miR-150-5p / SLC38A1 (solute carrier family 38 member 1) lipid ROS silencing of lncRNA ZFAS1 attenuated ferroptosis Silencing of lncRNA ZFAS1 attenuated ferroptosis and PF progression by lncRNA ZFAS1 acting as a competing endogenous RNA (ceRNA) and sponging miR-150-5p to downregulate SLC38A1 expression. lncRNA ZFAS1 promotes lung fibroblast-to-myofibroblast transition and ferroptosis via functioning as a ceRNA through miR-150- 5p/SLC38A1 axis 2020 32453709 GABPB1-AS1 ENSG00000244879 lncRNA cytoplasm H.sapiens Hepatocellular Carcinoma HepG2, Huh7 and Hep3B cell lines (up regulation) CCK-8 assay, lipid ROS assay, MDA assay Erastin, Ferrostatin-1 GABPB1 (GA binding protein transcription factor subunit beta 1) lipid ROS Decreased GABPB1 expression levels during ferroptosis GABPB1-AS1 was upregulated by erastin which inhibited the translation of GABPB1, leading to the inhibition of peroxidase gene expression and causing the accumulation of ROS and MDA and HepG2 cell death. LncRNA GABPB1-AS1 and GABPB1 regulate oxidative stress during erastin-induced ferroptosis in HepG2 hepatocellular carcinoma cells 2019 31700067 RP11-274B21.9 - lncRNA - H.sapiens Lung Cancer NCI-H1299 cell line (up regulation) RNA-seq - SLC7A11 System Xc- - The lncRNA function analysis revealed that the ferroptosis pathway, which was associated with SLC7A11, was one of the significant pathways affected. The downregulation of SLC7A11 induced by XAV939 may suppress the development of NSCLC via the ferroptosis pathway. RNA sequencing uncovers the key long non-coding RNAs and potential molecular mechanism contributing to XAV939-mediated inhibition of non-small cell lung cancer 2019 31186710 LINC00973 ENSG00000240476 lncRNA - H.sapiens Lung Cancer NCI-H1299 cell line (down regulation) RNA-seq - SLC7A11 System Xc- - The lncRNA function analysis revealed that the ferroptosis pathway, which was associated with SLC7A11, was one of the significant pathways affected. The downregulation of SLC7A11 induced by XAV939 may suppress the development of NSCLC via the ferroptosis pathway. RNA sequencing uncovers the key long non-coding RNAs and potential molecular mechanism contributing to XAV939-mediated inhibition of non-small cell lung cancer 2019 31186710 LINC00886 ENSG00000240875 lncRNA - H.sapiens Lung Cancer NCI-H1299 cell line (up regulation) RNA-seq - SLC7A11 System Xc- - The lncRNA function analysis revealed that the ferroptosis pathway, which was associated with SLC7A11, was one of the significant pathways affected. The downregulation of SLC7A11 induced by XAV939 may suppress the development of NSCLC via the ferroptosis pathway. RNA sequencing uncovers the key long non-coding RNAs and potential molecular mechanism contributing to XAV939-mediated inhibition of non-small cell lung cancer 2019 31186710 PCBP2-OT1 ENSG00000282977 lncRNA - H.sapiens Lung Cancer NCI-H1299 cell line (down regulation) RNA-seq - SLC7A11 System Xc- - The lncRNA function analysis revealed that the ferroptosis pathway, which was associated with SLC7A11, was one of the significant pathways affected. The downregulation of SLC7A11 induced by XAV939 may suppress the development of NSCLC via the ferroptosis pathway. RNA sequencing uncovers the key long non-coding RNAs and potential molecular mechanism contributing to XAV939-mediated inhibition of non-small cell lung cancer 2019 31186710 RP1-228H13.5 - lncRNA - H.sapiens Lung Cancer NCI-H1299 cell line RNA-seq - SLC7A11 System Xc- - The lncRNA function analysis revealed that the ferroptosis pathway, which was associated with SLC7A11, was one of the significant pathways affected. The downregulation of SLC7A11 induced by XAV939 may suppress the development of NSCLC via the ferroptosis pathway. RNA sequencing uncovers the key long non-coding RNAs and potential molecular mechanism contributing to XAV939-mediated inhibition of non-small cell lung cancer 2019 31186710 LINC00336 ENSG00000197251 lncRNA nucleus H.sapiens Lung Cancer H358 and PC9 cell lines (up regulation)A549 and SPC-A-1 cell lines (down regulation) MTT assay, iron assay, lipid ROS assay, MMP measurement, Mitosox Red staining, trypan blue staining Erastin, RSL3, Ferrostatin-1 miR-6852 / CBS transsulfuration pathway Overexpression of LINC00336 promotes cell growth, colony formation, tumor formation, and inhibits ferroptosis LINC00336 functions as an oncogene to facilitate tumor cell proliferation, inhibit ferroptosis, and induce tumor formation in an ELAVL1-dependent manner. Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA 2019 30787392 P53RRA ENSG00000233237 lncRNA cytoplasm H.sapiens Lung Cancer A549, SPCA1 and H522 cell lines (down regulation) HBE and H1299 cell lines (up regulation) MTT assay, iron and ferrous iron assay, C11-BODIPY staining, flow cytometry Erastin, Ferrostatin-1 G3BP1 lipid ROS P53RRA promoted ferroptosis LncRNAs can directly interact with the functional domain of signaling proteins in the cytoplasm, thus regulating p53 modulators to suppress cancer progression. A G3BP1-interacting lncRNA promotes ferroptosis and apoptosis in cancer via nuclear sequestration of p53 2018 29588351 ASMTL-AS1 ENSG00000236017 lncRNA nucleus and cytoplasm H.sapiens Lung Adenocarcinoma HLF-a, Calu-3, A549, NCI-H23 and SK-LU-1 CCK8 assay - SAT1 lipid ROS ASMTL-AS1 positively regulated SAT1 to promote ferroptosis mechanism assays were done to confirm the relationship among ASMTL-AS1, SAT1 and U2AF2. Results showed that ASMTL-AS1 was down-regulated in LUAD cells and ASMTL-AS1 up-regulation resulted in retarded LUAD cell and xenograft tumor growth along with stimulated ferroptosis. ASMTL-AS1 recruited U2AF2 to stabilize SAT1 mRNA. Furthermore, SAT1 exerted a cancer suppressor role in LUAD cells. ASMTL-AS1 impedes the malignant progression of lung adenocarcinoma by regulating SAT1 to promote ferroptosis 2021 34658100 H19 ENSG00000130600 lncRNA cytoplasm H.sapiens Breast Cancer MCF7 CCK8 assay erastin - glutathione assay kit lncRNA-H19 can regulate both autophagy and ferroptosis Autophagy inducers and H19 can reverse the production of lipid reactive oxygen species and the inhibition of autophagy induced by metformin. The present study suggests that metformin may induce ferroptosis by inhibiting autophagy via H19, and this discovery may facilitate the development of novel therapies for the treatment of breast cancer. Metformin may induce ferroptosis by inhibiting autophagy via lncRNA H19 in breast cancer 2021 34644456 hsa-miR-15a-3p MIMAT0004488 miRNA - H.sapiens Colorectal Cancer HCT-116, CaCo2, HT29, KM12 and NCM460 flow cytometer (Aceabio) erastin GPX4 GPX4 miR-15a-3p positively regulates ferroptosis Here we identified miR-15a-3p positively regulates ferroptosis via directly targeting glutathione peroxidase glutathione peroxidase 4 (GPX4) in CRC. Overexpression of miR-15a-3p repressed GPX4 through binding to the 3'-untranslated region of GPX4, resulting in increased reactive oxygen species level, intracellular Fe2+ level, and malondialdehyde accumulation in vitro and in vivo. Correspondingly, suppression of miR-15a-3p reduced the sensitivity of CRC cells to erastin and GPX4. Taken together, these data demonstrate that miR-15a-3p regulates ferroptosis through targeting GPX4 in CRC cells, illustrating the novel role of microRNA in ferroptosis. MiR-15a-3p regulates ferroptosis via targeting glutathione peroxidase GPX4 in colorectal cancer 2021 34727409 hsa-miR-539-5p MIMAT0003163 miRNA - H.sapiens Colorectal Cancer HCT116 and SW480 and the 293T CCK8 assay - TIPE GPX4 miR-539 promotes ferroptosis by targeting TIPE We aimed to investigate the functions and mechanisms of miR-539 in CRC proliferation. Functionally, miR-539 can bind to and regulate the expression of TIPE, and miR-539 activates SAPK/JNK to downregulate the expression of glutathione peroxidase 4 (GPX4) and promote ferroptosis. Our data reveal the novel role of miR-539 in regulating ferroptosis in CRC via activation of the SAPK/JNK axis, providing new insight into the mechanism of abnormal proliferation in CRC and a novel potential therapeutic target for advanced CRC. miR-539 activates the SAPK/JNK signaling pathway to promote ferropotosis in colorectal cancer by directly targeting TIPE 2021 34601499 hsa-miR-7-5p MIMAT0000252 miRNA - H.sapiens Clinically Relevant Radioresistant HeLa and SAS MitoSOXTM - ALOX12 lipid ROS miR-7-5p control radioresistance via ROS generation that leads to ferroptosis Knockdown of miR-7-5p increased reactive oxygen species (ROS), mitochondrial membrane potential, and intracellular Fe2+ amount. Furthermore, miR-7-5p knockdown results in the down-regulation of the iron storage gene expression such as ferritin, up-regulation of the ferroptosis marker ALOX12 gene expression, and increases of Liperfluo amount. H2O2 treatment after ALOX12 overexpression led to the enhancement of intracellular H2O2 amount and lipid peroxidation. By contrast, miR-7-5p knockdown seemed not to be involved in COX-2 and glycolysis signaling but affected the morphology of CRR cells. MiR-7-5p Is Involved in Ferroptosis Signaling and Radioresistance Thru the Generation of ROS in Radioresistant HeLa and SAS Cell Lines 2021 34361070 mmu-miR-15a MIMAT0000526 miRNA - mice Myocardial Infarctio hearts CCK8 assay - GPX4 GPX4 Over-expression of miR-15a-5p strengthened ferroptosis Silencing transcription factor early growth response-1 (Egr-1) inhibited the level of miR-15a-5p, increased the protein expression of GPX4, accompanied by reduced ferroptosis and alleviated myocardial injury. In summary, these results provide a novel signaling pathway during the progression of acute myocardial infarction, namely Egr-1/miR-15a-5p/GPX4/ferroptosis. The Egr-1/miR-15a-5p/GPX4 axis regulates ferroptosis in acute myocardial infarction 2021 34339707 hsa-miR-670-3p MIMAT0026640 miRNA - H.sapiens Glioblastoma U87MG and A172, SVGp12 and HA1800 CCK8 assay RSL3 or erastin ACSL4 lipid ROS microRNA-670-3p suppresses ferroptosis miR-670-3p level was elevated in human glioblastoma, but decreased upon ferroptotic stimulation. miR-670-3p inhibitor suppressed, while miR-670-3p mimic promoted glioblastoma cell growth through modulating ferroptosis. Mechanistically, ACSL4 was required for the regulation on ferroptosis and growth of glioblastoma cells by miR-670-3p. Moreover, U87MG and A172 cells treated with miR-670-3p inhibitor showed an increased chemosensitivity to TMZ. MicroRNA-670-3p suppresses ferroptosis of human glioblastoma cells through targeting ACSL4 2021 34323631 hsa-miR-302a-3p MIMAT0000684 miRNA - H.sapiens Non-Small Cell Lung Cancers A549, H358, H1299 and H1650 Ferrostain-1/erastin/RSL3 FPN lipid ROS miR-302a-3p induce ferroptosis of NSCLCs The miR-302a-3p mimic induced lipid peroxidation, iron overload and ferroptosis, thereby inhibiting cell growth and colony formation of NSCLCs cells. Conversely, the miR-302a-3p inhibitor block ederastin- or RSL3-related ferroptosis and tumor suppression. Additionally, we found that miR-302a-3p directly bound to the 3'-untranslational region of ferroportin to decrease its protein expression, and that ferroportin overexpression significantly prevented miR-302a-3p mimic-induced ferroptosis and tumor inhibition. Moreover, the miR-302a-3p mimic sensitized NSCLCs cells to cisplatin and paclitaxel chemotherapy. MicroRNA-302a-3p induces ferroptosis of non-small cell lung cancer cells via targeting ferroportin 2021 34181495 hsa-miR-382-5p MIMAT0000737 miRNA - H.sapiens Ovarian And Breast Cancer SKOV-3 and T47D Apoptosis Assay Kit lidocaine SLC7A11 lipid ROS inhibition of miR-382-5p blocked lidocaine-induced ferroptosis MiR-382-5p/SLC7A11 axis was involved in lidocaine-mediated inhibition of ovarian and breast cancer cell proliferation in vitro. The miR-382-5p expression was down-regulated but SLC7A11 expression was up-regulated in clinical ovarian and breast cancer samples. Furthermore, the treatment of lidocaine repressed tumor growth of ovarian cancer cells in vivo, in which the miR-382-5p expression was increased while SLC7A11 expression was decreased. Consequently, we concluded that the lidocaine promoted ferroptosis by miR-382-5p/SLC7A11 axis in ovarian and breast cancer cells. Lidocaine Promoted Ferroptosis by Targeting miR-382-5p /SLC7A11 Axis in Ovarian and Breast Cancer 2021 34122108 hsa-miR-130b-5p MIMAT0004680 miRNA - H.sapiens HTX1915, A375, G-361, HS1-CLS CCK8 assay erastin DKK1 lipid ROS miR-130b-3p to inhibit ferroptosis The results indicated that miR-130b-3p exerted an inhibitory role in erastin or RSL3-induced ferroptosis, evidenced by reductions in lipid peroxidation and ferrous ion content. By suppressing the expression of target gene DKK1, miR-130b-3p activated the Nrf2/HO-1 pathway, whereby repressing ferroptosis. miR-130b-3p blocked the antitumor activity of erastin. Further, in vitro findings were reproduced in an in vivo murine model. Together, these data suggest the potential of miR-130b-3p to inhibit ferroptosis in melanoma cells and the mechanism was related to DKK1-mediated Nrf2/HO-1 pathway. Suppressive role of microRNA-130b-3p in ferroptosis in melanoma cells correlates with DKK1 inhibition and Nrf2-HO-1 pathway activation 2021 34117611 hsa-miR-190a-5p MIMAT0000458 miRNA - H.sapiens Myocardial Infarction H9c2 cells and HEK-293 Lipid Peroxidation (MDA) Assay Kit erastin and RSL3 GLS2 lipid ROS miR-190a-5p negatively regulate ferroptosis We found that miR-190a-5p negatively regulate ferroptosis via directly targeting GLS2 in rat cardiomyocyte H9c2 cells. Forced expression of miR-190a-5p inhibited GLS2, resulting in downregulation of ROS, MDA and Fe 2+ accumulation. Meanwhile, inhibition of miR-190a-5p caused upregulation of GLS2, resulting in opposite effects which could be blocked by GLS2 inhibitor compound 968. miR-190a-5p regulates cardiomyocytes response to ferroptosis via directly targeting GLS2 2021 34111670 hsa-miR-375-3p MIMAT0000728 miRNA - H.sapiens Gastric Cancer SGC-7901 and BGC-823 CCK8 assay erastin, sorafenib, sulfasalazine SLC7A11 lipid ROS MiR-375 can trigger the ferroptosis microarray and bioinformatics analysis were performed to search the potential targets of miR-375 in GC cells. Luciferase reporter, RNA immunoprecipitation, and RNA-FISH assays were carried out to verify the targeting of miR-375. Subsequently, combined with tissue microarray analysis, erastin-resistant GC cells, transmission electron microscopy, a series of agonists and oxidative stress markers, the underlying mechanisms contributing to miR-375-mediated effects were explored. MiR-375 reduces the stemness of gastric cancer cells through triggering ferroptosis 2021 34090492 mmu-miR-122-5p MIMAT0000246 miRNA - Mouse Intracerebral Hemorrhage HT-22 cell CCK8 assay erastin TP53/SLC7A11 Lipid ROS IRN could alleviate ferroptosis-induced neurological damage after ICH through upregulating miR-122-5p Cells were treated with IRN following treatment with FAC after transfection with miR-122-5p inhibitor, and the results showed IRN reduced the FAC-induced decrease of miR-122-5p levels and relieved the ferroptosis by detecting ferroptotic marker proteins, iron ion concentration and oxidative stress level; after transfection with miR-122-5p inhibitor, the protective effects of IRN against FAC-induced ferroptosis in these cells were weakened. TP53 (also known as p53) was verified as a target of miR-122-5p by using dual luciferase reporter assay, and restoration of TP53 attenuated the effects of miR-122-5p on ferroptotic marker proteins expression, iron ion concentration and lipid ROS levels, as well as solute carrier family seven member 11 (SLC7A11) mRNA expression. Isorhynchophylline Relieves Ferroptosis-Induced Nerve Damage after Intracerebral Hemorrhage Via miR-122-5p/TP53/SLC7A11 Pathway 2021 33942214 hsa-miR-4443 MIMAT0018961 miRNA - H.sapiens Non-Small Cell Lung Carcinoma Exosomes CCK8 assay erastin METTL3 Lipid ROS miR-4443 inhibited FSP1-mediated ferroptosis Through bioinformatics analysis and luciferase assays, METTL3 was confirmed as a direct target gene of miR-4443. Further mechanistic analysis showed that miR-4443 regulated the expression of FSP1 in an m6A manner via METLL3. Exosomal miR-4443 promotes cisplatin resistance in non-small cell lung carcinoma by regulating FSP1 m6A modification-mediated ferroptosis 2021 33781830 circKDM4C - circRNA - H.sapiens Acute Myeloid Leukemia K-562 and HL-60 CCK8 assay erastin hsa-let-7b-5p/p53 Lipid ROS circKDM4C induces ferroptosis by sponging hsa-let-7b-5p We found that circKDM4C acts as a sponge of hsa-let-7b-5p and thereby regulates p53 which is a target gene of hsa-let-7b-5p. Also, the expression of circKDM4C and hsa-let-7b-5p are negatively correlated, while circKDM4C and p53 are positively correlated to AML patients. Moreover, we found that circKDM4C induces ferroptosis by sponging hsa-let-7b-5p which upregulates the expression of P53. CircKDM4C upregulates P53 by sponging hsa-let-7b-5p to induce ferroptosis in acute myeloid leukemia 2021 33733556 hsa-miR-101-3p MIMAT0000099 miRNA - H.sapiens Pulmonary Cancer A549, L78, NCI-H460, GLC-82, SPC-A1, and PC9 CCK8 assay - TBLR1 ROS miR-101-3p restores ferroptosis The expression levels of miR-101-3p and its target protein TBLR1 in tumour tissues and cells were detected, and their relationship with ferroptosis was clarified. Furthermore, the efficacy of nanocarriers in achieving in vivo therapeutic gene delivery was evaluated. Nanomedicine was further developed, with the anti-proliferative in vivo therapeutic effect validated using a subcutaneous xenograft cancer model. The expression level of miR-101-3p negatively correlated with clinical tumour size and TNM stage. miR-101-3p restores ferroptosis in tumour cells by directly targeting TBLR1, which in turn promotes apoptosis and inhibits proliferation. Nanomedicine promotes ferroptosis to inhibit tumour proliferation in vivo 2021 33674250 hsa-miR-324-3p MIMAT0000762 miRNA - H.sapiens Non Small Cell Lung Cancer A549/DDP CCK8 assay - GPX4 ROS miR-324-3p enhanced cisplatin-induced ferroptosis in the A549/DDP cells We identified the glutathione peroxidase 4 (GPX4) gene as the direct target of miR-324-3p, where overexpression of the gene reversed the miR-324-3p effect of sensitizing the A549/DDP cells to cisplatin. Furthermore, the GPX4 inhibitor RSL3 could mimic the effect of miR-324-3p upregulation in increasing the sensitivity of the cisplatin-resistant cells to the drug. Significantly, miR-324-3p enhanced cisplatin-induced ferroptosis in the A549/DDP cells. miR-324-3p reverses cisplatin resistance by inducing GPX4-mediated ferroptosis in lung adenocarcinoma cell line A549 2021 33662669 rno-miR-335 MIMAT0000575 miRNA - rats Parkinson'S Disease PC12 cells MMP assay - FTH1 ROS miR-335 enhanced ferroptosis The luciferase 3'-untranslated region reporter results identified FTH1 as the direct target of miR-335. The silencing of FTH1 in 6-OHDA-stimulated cells enhanced the effects of miR-335 on ferroptosis and promoted PD pathology. Mechanistically, miR-335 enhanced ferroptosis through the degradation of FTH1 to increase iron release, lipid peroxidation and reactive oxygen species (ROS) accumulation, and to decrease mitochondrial membrane potential (MMP). miR‑335 promotes ferroptosis by targeting ferritin heavy chain 1 in in vivo and in vitro models of Parkinson's disease 2021 33649797 hsa-miR-324-3p MIMAT0000762 miRNA - H.sapiens Breast Cancer MDA-MB-231 and MCF-7 BX53M fluorescence microscope erastin GPX4 ROS metformin induced ferroptosis by upregulating miR-324-3p Overexpression of miR-324-3p inhibited cancer cell viability. miR-324-3p inhibitor promoted cell viability. Further studies showed that the effect of miR-324-3p was mediated by directly targeting glutathione peroxidase 4 (GPX4). miR-324-3p bound to the 3ʹ-UTR of GPX4 and led to the downregulation of GPX4. In vivo studies showed that metformin induced ferroptosis by upregulating miR-324-3p in the xenograft model of breast cancer in mice. Metformin induces ferroptosis by targeting miR-324-3p/GPX4 axis in breast cancer 2021 33522578 rno-miR-23a-3p MIMAT0000792 miRNA - rats Intracerebral Hemorrhage Brain - - NFE2L2 ROS miR-23a-3p Inhibition Attenuates the Ferroptosis Acupuncture also alleviated ferroptosis and decreased miR-23a-3p expression, as evidenced by the increased NFE2L2 nuclear translocation and expressions of heme oxygenase-1 and glutathione peroxidase 4 and the decreased iron and malondialdehyde contents and reactive oxygen species accumulation. Additionally, antagomiR-23a-3p inhibited the ICH-induced increases in FJB-positive cells, release of proinflammatory cytokines, ferroptosis, and promoted NFE2L2 activation. Notably, the binding site of miR-23a-3p existed in NFE2L2. Taken together, acupuncture may alleviate the neuronal cell death, inflammation, and ferroptosis after ICH by down-regulating miR-23a-3p. Acupuncture Ameliorates Neuronal Cell Death, Inflammation, and Ferroptosis and Downregulated miR-23a-3p After Intracerebral Hemorrhage in Rats 2021 33403590 hsa-miR-10a-5p MIMAT0000253 miRNA - H.sapiens Intervertebral Disc Degeneration chondrocytes DCFH-DA - IL-6R ROS Overexpressing miR-10a-5p suppressed IL-6R expression, and partially abolished IL-6-induced ferroptosis Results from current study suggests that inflammatory cytokine IL-6 appeared in IVD aggravates its degeneration by inducing cartilage cell ferroptosis. This is caused partially by inhibiting miR-10a-5p and subsequently derepressing IL-6R signaling pathway. Our study provides a novel mechanism explaining inflammatory cytokine-caused cartilage cell death in degenerative IVD, and makes IL-6/miR-10a-5p/IL-6R axis a potential therapeutic target for intervention of IDD. Targeting miR-10a-5p/IL-6R axis for reducing IL-6-induced cartilage cell ferroptosis 2020 33166496 mmu-miR-182-5p MIMAT0000211 miRNA - mouse Ischemia/Reperfusion (I/R) Kidney Injury TCMK-1 Iron Assay Kit (Abcam) erastin/ferrostatin-1 GPX4 ROS miR-182-5p and miR-378a-3p induced ferroptosis We identified that miR-182-5p and miR-378a-3p were upregulated in the ferroptosis and H/R-induced injury, and correlates reversely with glutathione peroxidases 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) expression in renal I/R injury tissues, respectively. In vitro studies showed that miR-182-5p and miR-378a-3p induced ferroptosis in cells. We further found that miR-182-5p and miR-378a-3p regulated the expression of GPX4 and SLC7A11 negatively by directly binding to the 3'UTR of GPX4 and SLC7A11 mRNA. In vivo study showed that silencing miR-182-5p and miR-378a-3p alleviated the I/R-induced renal injury in rats. miR-182-5p and miR-378a-3p regulate ferroptosis in I/R-induced renal injury 2020 33116120 mmu-miR-378a-3p MIMAT0003151 miRNA - mouse Ischemia/Reperfusion (I/R) Kidney Injury TCMK-1 Iron Assay Kit (Abcam) erastin/ferrostatin-1 SLC7A11 ROS miR-182-5p and miR-378a-3p induced ferroptosis We identified that miR-182-5p and miR-378a-3p were upregulated in the ferroptosis and H/R-induced injury, and correlates reversely with glutathione peroxidases 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) expression in renal I/R injury tissues, respectively. In vitro studies showed that miR-182-5p and miR-378a-3p induced ferroptosis in cells. We further found that miR-182-5p and miR-378a-3p regulated the expression of GPX4 and SLC7A11 negatively by directly binding to the 3'UTR of GPX4 and SLC7A11 mRNA. In vivo study showed that silencing miR-182-5p and miR-378a-3p alleviated the I/R-induced renal injury in rats. miR-182-5p and miR-378a-3p regulate ferroptosis in I/R-induced renal injury 2020 33116120 hsa-miR-137-3p MIMAT0000429 miRNA - H.sapiens Neuroblastoma SH-SY5Y cells MTT assay oxyHb COX2/PGE2 ROS decrease in miR-137 levels and inhibit ferroptosis miR-137 overexpression boosts the neuroprotective effects of EPC-EXs against apoptosis and mitochondrial dysfunction in oxyHb-treated SH-SY5Y cells. Furthermore, EXsmiR-137 rather than EXs can restore the decrease in miR-137 levels and inhibit ferroptosis, and the protection mechanism might involve the miR-137-COX2/PGE2 signaling pathway. miR-137 boosts the neuroprotective effect of endothelial progenitor cell-derived exosomes in oxyhemoglobin-treated SH-SY5Y cells partially via COX2/PGE2 pathway 2020 33100224 hsa-miR-424-5p MIMAT0001341 miRNA - H.sapiens Ovarian Cancer ovarian iron assay kit erastin ACSL4 ACSL4 miR-424-5p regulates ferroptosis by targeting ACSL4 in ovarian cancer cells We show that miR-424-5p negatively regulates ferroptosis by directly targeting ACSL4 in ovarian cancer cells. Upregulation of miR-424-5p suppressed ACSL4 by directly binding to its 3'-UTR, which subsequently reduced erastin- and RSL3-induced ferroptosis. Meanwhile, knockdown of miR-424-5p increased the sensitivity of ovarian cancer cells to erastin and RSL3. Furthermore, ACSL4 was upregulated in ovarian cancer tissues, and high ACSL4 expression predicted worse prognosis and sensitized ovarian cancer cells to erastin- and RSL3-induced ferroptosis. Importantly, decreases in lipid peroxides and ferroptotic cell death mediated by miR-424-5p could be abrogated by ACSL4 overexpression. Tumor suppressor miR-424-5p abrogates ferroptosis in ovarian cancer through targeting ACSL4 2020 33038905 hsa-miR-522 MI0003177 miRNA exosomes H.sapiens Gastric Cancer cancer-associated fibroblast (CAF) cell lines (up regulation) mass spectrum, RT-qPCR, lipid ROS assay, MMP measurement Erastin ALOX15 (arachidonate lipoxygenase 15) lipid ROS miR-522 suppresses ferroptosis CAFs secrete exosomal miR-522 to inhibit ferroptosis in cancer cells by targeting ALOX15 and blocking lipid-ROS accumulation. Importantly, cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis and ultimately result in decreased chemo-sensitivity. CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer 2020 32106859 hsa-miR-214 MI0000290 miRNA - H.sapiens Hepatoma HepG2 and Hep3B cell lines (down regulation) CCK-8 assay, colony formation assay, iron assay, MDA assay, DCFH-DA staining, flow cytometry Erastin, Ferrostatin-1 ATF4 (transcription factor 4) lipid ROS microRNA-214-3p enhances erastin-induced ferroptosis The ferroptosis-promoting effects of miR-214 in hepatoma cells are attributed at least to its inhibitory effects on ATF4, which may provide a new target for therapy of hepatoma regarding ferroptosis. MicroRNA-214-3p enhances erastin-induced ferroptosis by targeting ATF4 in hepatoma cells 2020 31960438 hsa-miR-30b-5p MIMAT0000420 miRNA - H.sapiens Preeclampsia HTR-8/SVneo and TEV-1 H2DCFDA - Pax3/SLC7A11 GPX4 upregulation of miR-30b-5p in PE models plays a pivotal role in ferroptosis Microarrays, bioinformatic analysis, and luciferase reporter assay revealed that upregulation of miR-30b-5p in PE models plays a pivotal role in ferroptosis, by downregulating Cys2/glutamate antiporter and PAX3 and decreasing ferroportin 1 (an iron exporter) expression, resulting in decreased GSH and increased labile Fe2+. Inhibition of miR-30b-5p expression and supplementation with ferroptosis inhibitors attenuated the PE symptoms in rat models, making miR-30b-5p a potential therapeutic target for PE. miR-30-5p-mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsia 2020 31926626 hsa-miR-4715-3p MIMAT0019825 miRNA - H.sapiens Gastric Cancer, Esophagus Cancer OE33, MKN45 and STKM2 cell lines (down regulation) western blot, qRT-PCR, luciferase reporter assay, flow cytometry - AURKA (Aurora kinase A) GPX4 miR-4715-3p inhibited GPX4 and induced cell death, suggesting a link between AURKA and ferroptosis Inhibition of AURKA or reconstitution of miR-4715-3p induced cell death and inhibited GPX4. miR-4715-3p reconstitution enhanced cisplatin sensitivity. Epigenetic regulation of AURKA by miR-4715-3p in upper gastrointestinal cancers 2019 31740746 hsa-miR-103a-3p MIMAT0000101 miRNA - H.sapiens Gastric Cancer MGC-803 and MKN-45 cell lines (up regulation) CCK-8 assay, lipid ROS assay, MDA assay, iron assay Erastin, Ferrostatin-1 GLS2 (glutaminase 2) glutamine metabolism PG exerts pro-ferroptosis and anti-tumor effects in vitro and in vivo through regulating miR-103a-3p/GLS2 axis PG treatment significantly promoted ferroptosis and anti-tumorigenesis by down-regulating inhibitory effect of miR-103a-3p on GLS2 expression. Physcion 8-O-β-glucopyranoside induced ferroptosis via regulating miR-103a-3p/GLS2 axis in gastric cancer 2019 31606381 hsa-miR-212-5p MIMAT0022695 miRNA extracellular vesicle mice Tbi (Traumatic Brain Injury) HT-22 and Neuro-2a cell lines (down regulation) qRT-PCR, western blot, iron assay, MDA assay RSL3, Ferrostatin-1 Ptgs2 (prostaglandin-endoperoxide synthase-2) lipid ROS overexpression of miR-212-5p attenuated ferroptosis miR-212-5p was significantly downregulated after TBI and functionally suppressed ferroptosis by directly targeting Ptgs2. Administration of miR-212-5p in CCI mice significantly improved learning and spatial memory. miR-212-5p attenuates ferroptotic neuronal death after traumatic brain injury by targeting Ptgs2 2019 31533781 hsa-miR-7-5p MIMAT0000252 miRNA - H.sapiens Cervical Cancer, Tongue Squamous Carcinoma, Hepatoma CRR (clinically relevant radioresistant) cells in HeLa, SAS and HepG2 cell lines (up regulation) FerroOrange - - iron metabolism miR-7-5p downregulates mitoferrin and reduces Fe2+, which influences ferroptosis MiR-7-5p may control radioresistance in various cancer cells at the clinically relevant dose of irradiation. MiR-7-5p downregulates mitoferrin and reduces Fe2+, which influences ferroptosis. MiR-7-5p is a key factor that controls radioresistance via intracellular Fe2+ content in clinically relevant radioresistant cells 2019 31472959 hsa-miR-17 MI0000071 miRNA endothelial cell H.sapiens - HUVEC cell line (up regulation) CCK-8 assay, C11-BODIPY staining, flow cytometry Erastin, Ferrostatin-1 A20 (known as TNFAIP3) / ACSL4 lipid ROS miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis This study revealed a novel mechanism through which miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis. miRNA-17-92 protects endothelial cells from erastin-induced ferroptosis through targeting the A20-ACSL4 axis 2019 31160087 hsa-miR-18a MI0000072 miRNA endothelial cell H.sapiens - HUVEC cell line (up regulation) CCK-8 assay, C11-BODIPY staining, flow cytometry Erastin, Ferrostatin-1 A20 (known as TNFAIP3) / ACSL4 lipid ROS miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis This study revealed a novel mechanism through which miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis. miRNA-17-92 protects endothelial cells from erastin-induced ferroptosis through targeting the A20-ACSL4 axis 2019 31160087 hsa-miR-19a MI0000073 miRNA endothelial cell H.sapiens - HUVEC cell line (up regulation) CCK-8 assay, C11-BODIPY staining, flow cytometry Erastin, Ferrostatin-1 A20 (known as TNFAIP3) / ACSL4 lipid ROS miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis This study revealed a novel mechanism through which miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis. miRNA-17-92 protects endothelial cells from erastin-induced ferroptosis through targeting the A20-ACSL4 axis 2019 31160087 hsa-miR-20a MI0000076 miRNA endothelial cell H.sapiens - HUVEC cell line (up regulation) CCK-8 assay, C11-BODIPY staining, flow cytometry Erastin, Ferrostatin-1 A20 (known as TNFAIP3) / ACSL4 lipid ROS miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis This study revealed a novel mechanism through which miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis. miRNA-17-92 protects endothelial cells from erastin-induced ferroptosis through targeting the A20-ACSL4 axis 2019 31160087 hsa-miR-19b MI0000074 miRNA endothelial cell H.sapiens - HUVEC cell line (up regulation) CCK-8 assay, C11-BODIPY staining, flow cytometry Erastin, Ferrostatin-1 A20 (known as TNFAIP3) / ACSL4 lipid ROS miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis This study revealed a novel mechanism through which miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis. miRNA-17-92 protects endothelial cells from erastin-induced ferroptosis through targeting the A20-ACSL4 axis 2019 31160087 hsa-miR-92 - miRNA endothelial cell H.sapiens - HUVEC cell line (up regulation) CCK-8 assay, C11-BODIPY staining, flow cytometry Erastin, Ferrostatin-1 A20 (known as TNFAIP3) / ACSL4 lipid ROS miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis This study revealed a novel mechanism through which miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis. miRNA-17-92 protects endothelial cells from erastin-induced ferroptosis through targeting the A20-ACSL4 axis 2019 31160087 hsa-miR-9 - miRNA - H.sapiens Melanoma A375 and G-361 cell lines (up regulation) CCK-8 assay, MDA assay, iron assay, glutamate assay, glutamine assay, a-KG assay Erastin, RSL3, Ferrostatin-1 GOT1 glutaminolysis miR-9 regulates ferroptosis by targeting GOT1 Overexpression of miR-9 suppressed GOT1 by directly binding to its 3'-UTR, which subsequently reduced erastin- and RSL3-induced ferroptosis. miR-9 regulates ferroptosis by targeting glutamic-oxaloacetic transaminase GOT1 in melanoma 2018 30035324 hsa-miR-137 MI0000454 miRNA - H.sapiens Melanoma A375 and G-361 cell lines (up regulation) CCK-8 assay, MDA assay, C11-BODIPY staining, flow cytometry, iron assay, glutamine uptake assay Erastin, RSL3, Ferrostatin-1 SLC1A5 glutaminolysis knockdown of miR-137 increased the antitumor activity of erastin by enhancing ferroptosis MiR-137 negatively regulates ferroptosis by directly targeting glutamine transporter SLC1A5 in melanoma cells. miR-137 regulates ferroptosis by targeting glutamine transporter SLC1A5 in melanoma 2018 29348676 hsa-miR-27a-3p MIMAT0000084 miRNA - H.sapiens Non-Small Cell Lung Cancer Beas-2B CCK-8 assay erastin SLC7A11 ROS miR-27a-3p modulated ferroptosis by targeting SLC7A11 in NSCLC cells miR-27a-3p, was an essential modulator of ferroptosis via directly targeting SLC7A11 in NSCLC cells. Overexpressing miR-27a-3p led to SLC7A11 suppression via directly binding to its 3'-UTR, followed by the reduction of erastin-caused ferroptosis. In contrast, inhibited miR-27a-3p resulted in an increase in NSCLC cells' sensitivity to erastin. Of importance, the accumulated lipid ROS and cell death of iron peptide mediated by anti-miR-27a-3p can be eliminated by impeding the glutamylation process. MiR-27a-3p Promotes Non-Small Cell Lung Cancer Through SLC7A11-Mediated-Ferroptosis 2021 34722314 hsa-miR-5096 MIMAT0020603 miRNA - H.sapiens Breast Cancer MDA-MB-468, MDA-MB-453, BT-549, MDAMB-231, SKBR-3, T-47D, MCF-7, and ZR-75 and a normal epithelial breast cell line, MCF-10A ferene assay erastin SLC7A11/ xCT SLC7A11 miR-5096-induced ferroptotic cell death We demonstrated SLC7A11 as a target of miR-5096 by 3'UTR luciferase assay and further validated it by identifying reduced mRNA and protein levels of SLC7A11 upon miR-5096 overexpression. miR-5096-induced ferroptotic cell death in human breast cancer cells was confirmed by concurrently increased ROS, OH-, lipid ROS, and iron accumulation levels and decreased GSH and mitochondrial membrane potential with mitochondrial shrinkage and partial cristae loss. SLC7A11/ xCT is a target of miR-5096 and its restoration partially rescues miR-5096-mediated ferroptosis and anti-tumor effects in human breast cancer cells 2021 34571083 hsa-miR-34a-5p MIMAT0000255 miRNA - H.sapiens PC12 MTT assay/DCFH-DA Sirt1 lipid ROS Knock-down of miR-34a-5p mitigates CdCl2-induced ferroptosis The molecular mechanisms leading to apoptosis and ferroptosis at least included the participation of the miR-34a-5p/Sirt1 axis, in which miR-34a-5p promoted CdCl2 -induced neurotoxicity through targeting Sirt1. Knocking out miR-34a-5p attenuated CdCl2 -induced damage of PC12 cells, cytotoxicity and neurotoxicity. Cadmium induces ferroptosis and apoptosis by modulating miR-34a-5p/Sirt1axis in PC12 cells 2021 34558789 mmu-miR-124-3p MIMAT0000134 miRNA - Mouse Aged Intracerebral Hemorrhage Serum - - Fpn - miR124/Fpn signaling may mediate the outcome of ICH through apoptosis and ferroptosis Based on prediction of website tools, expression level of potential miRNAs in ICH tissues and results of luciferase reporter assays, miR-124 was identified to regulate Fpn expression post-ICH. Higher serum miR-124 levels were correlated with poor neurologic scores of aged ICH patients. Administration of miR-124 antagomir enhanced Fpn expression and attenuated iron accumulation in aged mice model. Both apoptosis and ferroptosis, but not necroptosis, were regulated by miR-124/Fpn signaling manipulation. Targeting miR-124/Ferroportin signaling ameliorated neuronal cell death through inhibiting apoptosis and ferroptosis in aged intracerebral hemorrhage murine model 2020 33068460 hsa-miR-19b-3p MIMAT0000074 miRNA - H.sapiens Colorectal Cancer CaCO2 cell line (up regulation) miScript System (miRNA PCR Array miFinder) Erastin ACSL4 lipid ROS elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2 cells compared to in DLD-1 cells potentially targeted ACSL-4 Interactome analysis between these down-regulated gene and up-regulated miRNAs altered by bromelain in CaCO2 cells compared to in DLD-1 cells indicated that ACSL-4 is a key regulatory molecule. Bromelain effectively suppresses Kras-mutant colorectal cancer by stimulating ferroptosis 2018 30460115 hsa-miR-130a-3p MIMAT0000425 miRNA - H.sapiens Colorectal Cancer CaCO2 cell line (up regulation) miScript System (miRNA PCR Array miFinder) Erastin ACSL4 lipid ROS elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2 cells compared to in DLD-1 cells potentially targeted ACSL-4 Interactome analysis between these down-regulated gene and up-regulated miRNAs altered by bromelain in CaCO2 cells compared to in DLD-1 cells indicated that ACSL-4 is a key regulatory molecule. Bromelain effectively suppresses Kras-mutant colorectal cancer by stimulating ferroptosis 2018 30460115 hsa-miR-150-5p MIMAT0000451 miRNA - H.sapiens Colorectal Cancer CaCO2 cell line (up regulation) miScript System (miRNA PCR Array miFinder) Erastin ACSL4 lipid ROS elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2 cells compared to in DLD-1 cells potentially targeted ACSL-4 Interactome analysis between these down-regulated gene and up-regulated miRNAs altered by bromelain in CaCO2 cells compared to in DLD-1 cells indicated that ACSL-4 is a key regulatory molecule. Bromelain effectively suppresses Kras-mutant colorectal cancer by stimulating ferroptosis 2018 30460115 hsa-miR-144-3p MIMAT0000436 miRNA - H.sapiens Colorectal Cancer CaCO2 cell line (up regulation) miScript System (miRNA PCR Array miFinder) Erastin ACSL4 lipid ROS elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2 cells compared to in DLD-1 cells potentially targeted ACSL-4 Interactome analysis between these down-regulated gene and up-regulated miRNAs altered by bromelain in CaCO2 cells compared to in DLD-1 cells indicated that ACSL-4 is a key regulatory molecule. Bromelain effectively suppresses Kras-mutant colorectal cancer by stimulating ferroptosis 2018 30460115 hsa-miR-16-5p MIMAT0000069 miRNA - H.sapiens Colorectal Cancer CaCO2 cell line (up regulation) miScript System (miRNA PCR Array miFinder) Erastin ACSL4 lipid ROS elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2 cells compared to in DLD-1 cells potentially targeted ACSL-4 Interactome analysis between these down-regulated gene and up-regulated miRNAs altered by bromelain in CaCO2 cells compared to in DLD-1 cells indicated that ACSL-4 is a key regulatory molecule. Bromelain effectively suppresses Kras-mutant colorectal cancer by stimulating ferroptosis 2018 30460115 hsa-miR-7a-5p - miRNA - H.sapiens Colorectal Cancer CaCO2 cell line (up regulation) miScript System (miRNA PCR Array miFinder) Erastin ACSL4 lipid ROS elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2 cells compared to in DLD-1 cells potentially targeted ACSL-4 Interactome analysis between these down-regulated gene and up-regulated miRNAs altered by bromelain in CaCO2 cells compared to in DLD-1 cells indicated that ACSL-4 is a key regulatory molecule. Bromelain effectively suppresses Kras-mutant colorectal cancer by stimulating ferroptosis 2018 30460115 hsa-miR-17-5p MIMAT0000070 miRNA - H.sapiens Colorectal Cancer CaCO2 cell line (up regulation) miScript System (miRNA PCR Array miFinder) Erastin ACSL4 lipid ROS elevated miR-19b-3p, -130a-3p, -150-5p, -144-3p, -16-5p, -7a-5p, and -17-5p in bromelain-treated CaCO2 cells compared to in DLD-1 cells potentially targeted ACSL-4 Interactome analysis between these down-regulated gene and up-regulated miRNAs altered by bromelain in CaCO2 cells compared to in DLD-1 cells indicated that ACSL-4 is a key regulatory molecule. Bromelain effectively suppresses Kras-mutant colorectal cancer by stimulating ferroptosis 2018 30460115 NEAT1 ENSG00000245532 lncRNA - Homo sapiens (human) Hepatocellular carcinoma HEK293T and HepG2 CCK-8 assay erastin miR-362-3p/MIOX ROS NEAT1 can increasing the sensitivity of HCC cells to ferroptosis We found that ferroptosis inducers erastin and RSL3 increased NEAT1 expression by promoting the binding of p53 to the NEAT1 promoter. Induced NEAT1 promoted the expression of MIOX by competitively binding to miR-362-3p. MIOX increased ROS production and decreased the intracellular levels of NADPH and GSH, resulting in enhanced erastin- and RSL3-induced ferroptosis. Importantly, overexpression of NEAT1 increased the anti-tumor activity of erastin and RSL3 by enhancing ferroptosis both in vitro and in vivo. Long noncoding RNA NEAT1 promotes ferroptosis by modulating the miR-362-3p/MIOX axis as a ceRNA 2022 35338333 hsa-miR-23a-3p MIMAT0000078 miRNA - Homo sapiens (human) Hepatocellular carcinoma PLC/PRF/5 cell line MTT assay ferrostatin-1 ACSL4 ROS MiR-23a-3p acted as a direct suppressor of ferroptosis CRISPR-Cas9 knockout of miR-23a-3p improved sorafenib response in HCC cells as well as orthotopic HCC tumours. Proteomics analysis suggested that sorafenib-induced ferroptosis was the key pathway suppressed by miR-23a-3p with reduced cellular iron accumulation and lipid peroxidation. MiR-23a-3p directly targeted the 3′-untranslated regions (UTR) of ACSL4, the key positive regulator of ferroptosis. The miR-23a-3p inhibitor rescued ACSL4 expression and induced ferrotoptic cell death in sorafenib-treated HCC cells. The co-delivery of ACSL4 siRNA and miR-23a-3p inhibitor abolished sorafenib response. Epigenetic regulation of ferroptosis via ETS1/miR-23a-3p/ACSL4 axis mediates sorafenib resistance in human hepatocellular carcinoma 2022 34980204 H19 ENSG00000130600 lncRNA - Homo sapiens (human) Lung cancer H1299 and H460 GSH Assay Kit curcumenol miR-19b-3p/FTH1 GSH Loss of lncRNA H19 leads to ferroptotic cell death Overexpression of lncRNA H19 eliminated the anticancer effect of curcumenol, while lncRNA H19 knockdown promoted ferroptosis induced by curcumenol treatment. Mechanistically, we showed that lncRNA H19 functioned as a competing endogenous RNA to bind to miR-19b-3p, thereby enhanced the transcription activity of its endogenous target, ferritin heavy chain 1 (FTH1), a marker of ferroptosis. In conclusion, our data show that the natural product curcumenol exerted its antitumor effects on lung cancer by triggering ferroptosis, and the lncRNA H19/miR-19b-3p/FTH1 axis plays an essential role in curcumenol-induced ferroptotic cell death. Curcumenol triggered ferroptosis in lung cancer cells via lncRNA H19/miR-19b-3p/FTH1 axis 2022 35224289 hsa-miR-23a-3p MIMAT0000078 miRNA exosome Homo sapiens (human) Acute myocardial infarction Blood CCK8 assay - DMT1 GSH HUCB-MSCs-exosomes may suppress DMT1 expression by miR-23a-3p to inhibit ferroptosis HUCB- MSCs-derived exosomes inhibited ferroptosis and re- duced myocardial injury, which was abolished in exosome obtained from HUCB-MSCs with miR-23a- 3p inhibition. Our studies suggest that exosomes from HUCB-MSCs suppressed the ferroptosis of cardiomyo- cyte to mediate myocardial repair in AMI mice via delivering miR-23a-3p. Human umbilical cord blood-derived MSCs exosome attenuate myocardial injury by inhibiting ferroptosis in acute myocardial infarction mice 2020 32535745 hsa-miR-124-3p MIMAT0000422 miRNA exosome Homo sapiens (human) Ischemia-reperfusion injury Bone marrow mesenchymal stem cells CCK-8 assays - STEAP3 GSH and GPX4 miR-124-3p in HM-exos downregulates Steap3 expression to inhibit ferroptosis In vitro, inhibition of ferroptosis by HM-exos reduced hepatocyte injury. HM-exos contained more abundant miR-124-3p, which reduced ferroptosis of H/R-treated cells by inhibiting prostate six transmembrane epithelial antigen 3 (STEAP3), while overexpression of Steap3 reversed the effect of mir-124-3p. In addition, HM-exos from cell knocked out for miR-124-3p showed a weakened inhibitory effect on ferroptosis. Similarly, HM-exo treatment increased the content of miR-124-3p in grafts, while decreasing the level of STEAP3 and reducing the degree of hepatic ferroptosis. miR-124-3p delivered by exosomes from heme oxygenase-1 modified bone marrow mesenchymal stem cells inhibits ferroptosis to attenuate ischemia-reperfusion injury in steatotic grafts 2022 35459211 circPtpn14 mmu_circ_0000130 circRNA - Homo sapiens (human) Traumatic brain injury Brain CCK-8 assays - miR-351-5p/5-LOX ROS circPtpn14 overexpression partly abolished the inhibitory effects of melatonin on ferroptosis circPtpn14 functions as miR-351-5p sponges to suppress the miRNA. Meanwhile, miR-351-5p could also target 5-LOX for mRNA degradation. CircPtpn14/miR-351-5p/5-LOX signaling may be one of the molecular mechanisms regulating ferroptosis. A novel mechanism linking ferroptosis and endoplasmic reticulum stress via the circPtpn14/miR-351-5p/5-LOX signaling in melatonin-mediated treatment of traumatic brain injury 2022 34883251 hsa-miR-140-5p MIMAT0000431 miRNA exosome Homo sapiens (human) Obesity-induced cardiac injury H9c2 myocardial cells GSH Assay Kit ferrostatin-1 SLC7A11 GSH Attenuating exosomal-miR-140-5p expression alleviates ferroptosis miR-140-5p is abundant in obese ATM-Exos and promotes ferroptosis in cardiomyocytes. Solute carrier family 7 member 11 (SLC7A11) is a downstream target of miR-140-5p, which induces ferroptosis via inhibition of GSH synthesis by targeting SLC7A11. Attenuating exosomal-miR-140-5p expression alleviates ferroptosis and cardiac injury induced by obese ATM exosomes by alleviating GSH inhibition. Adipose tissue macrophage-derived exosomes induce ferroptosis via glutathione synthesis inhibition by targeting SLC7A11 in obesity-induced cardiac injury 2022 35271999 NEAT1 ENSG00000245532 lncRNA exosome rat Sepsis Brain CCK-8 assay FeCl3 TFRC GSH and GPX4 Overexpression of NEAT1 enhanced ferroptosis In vitro, it is found that NEAT1 functions as a ceRNA for miR-9-5p to facilitate TFRC and GOT1 expression. Overexpression of NEAT1 enhanced ferroptosis stress in bEnd.3 cells. Increased miR-9-5p alleviated sepsis-induced ferroptosis by suppressing the expression of TFRC and GOT1 both in vivo and in vitro. Exosome-Derived lncRNA NEAT1 Exacerbates Sepsis-Associated Encephalopathy by Promoting Ferroptosis Through Regulating miR-9-5p/TFRC and GOT1 Axis 2022 35038133 hsa-miR-6077 MIMAT0023702 miRNA cytoplasm Homo sapiens (human) Lung adenocarcinoma H358 and H1299 CellTiter-Lumi kit CDDP/PEM KEAP1 ROS miR-6077 targets KEAP1, thus decreasing ferroptosis We demonstrated that miR-6077 protects LUAD cells from cell death induced by CDDP/PEM via CDKN1A-CDK1-mediated cell-cycle arrest and KEAP1-NRF2-SLC7A11/NQO1-mediated ferroptosis, thus resulting in chemoresistance in multiple LUAD cells both in vitro and in vivo. Moreover, we found that GMDS-AS1 and LINC01128 sensitized LUAD cells to CDDP/PEM by sponging miR-6077. Collectively, these results imply the critical role of miR-6077 in LUAD's sensitivity to CDDP/PEM, thus providing a novel therapeutic strategy for overcoming chemoresistance in clinical practice. miR-6077 promotes cisplatin/pemetrexed resistance in lung adenocarcinoma via CDKN1A/cell cycle arrest and KEAP1/ferroptosis pathways 2022 35505963 mmu_circRNA_0000309 mmu_circRNA_0000309 circRNA - mouse Diabetic nephropathy MPC5 Glutathione Peroxidase Cellular Activity Assay Kit high glucose miR-188-3p/GPX4 GPX4 mmu_circRNA_0000309 sponges miR-188-3p, and subsequently upregulates GPX4 expression, inactivating ferroptosis-dependent mitochondrial function mmu_mmu_circRNA_0000309, located in host gene vascular endothelial zinc finger 1 (Vezf1), showed a sharp decline in DN mice and a remarkable recovery in germacrone-challenged DN mice. mmu_circRNA_0000309 silence or miR-188-3p mimics abrogated the antiapoptosis and anti-injury effects of germacrone through aggravating mitochondria damage, and elevating reactive oxygen species and ferroptosis-related protein levels. Mechanistically, mmu_circRNA_0000309 competitively sponged miR-188-3p, and subsequently promoted glutathione peroxidase 4 (GPX4) expression, thereby inactivating ferroptosis-dependent mitochondrial damage and podocyte apoptosis. A Novel Identified Circular RNA, mmu_mmu_circRNA_0000309, Involves in Germacrone-Mediated Improvement of Diabetic Nephropathy Through Regulating Ferroptosis by Targeting miR-188-3p/GPX4 Signaling Axis 2022 34913724 hsa-miR-1287-5p MIMAT0005878 miRNA - Homo sapiens (human) Osteosarcoma hFOB1.19 CCK-8 assay erastin GPX4 GSH and GPX4 miR-1287-5p promotes ferroptosis o miR-1287-5p expression was downregulated in human osteosarcoma, but upregulated upon ferroptotic stimulation. Overexpression of miR-1287-5p significantly induced, while inhibition of miR-1287-5p suppressed ferroptosis of osteosarcoma cells, thereby modulating cell viability and colony formation. Mechanistic studies indicated that miR-1287-5p directly bound to the 3'-untranslated region of glutathione peroxidase 4 (GPX4) to inhibit its protein level and activity, and that GPX4 overexpression completely abolished the miR-1287-5p mimic-mediated ferroptotic induction and tumor suppression. Moreover, the miR-1287-5p mimic dramatically sensitized human osteosarcoma cells to cisplatin chemotherapy. MicroRNA-1287-5p promotes ferroptosis of osteosarcoma cells through inhibiting GPX4 2021 35038953 rno-miR-23a-3p MIMAT0000792 miRNA exosome rat Atrial fibrillation h9c2 cells Western blotting fer-1 SLC7A11 ROS CF-exos-miR-23a-3p may promote ferroptosis Our results demonstrated that pacing-CF-exos highly expressed miR-23a-3p by informatics analysis and experimental verification. Inhibitor-miR-23a-3p protected h9c2 cells from ferroptosis accompanying with upregulation of SLC7A11. In addition, SLC7A11 was shown to be the target gene of miR-23a-3p. In conclusion, our results suggest that CF-exos-miR-23a-3p may promote ferroptosis. The development of AF in a persistent direction could be prevented by intervening with exosomal miRNAs to reduce oxidative stress injury and ferroptosis. Cardiac Fibroblasts Promote Ferroptosis in Atrial Fibrillation by Secreting Exo-miR-23a-3p Targeting SLC7A11 2022 35677105 hsa-miR-15a MIMAT0000068 miRNA - Homo sapiens (human) Prostate cancer LNCAP MDA Assay kit - GPX4 GPX4 miR-15a induces ferroptosis The results demonstrated that transfection with miR-15a mimics decreased GPX4 protein expression. Bioinformatics analysis revealed potential binding sites between miR-15a and the 3′-UTR region of GPX4, and RNA pull-down and the dual-luciferase reporter assays further confirmed the interaction between miR-15a and GPX4 mRNA. Both transfection with miR-15a mimics and si-GPX4 suppressed cell proliferation, elevated LDH release, accumulated intracellular ferrous iron and ROS, disrupted MMP and increased MDA levels. Taken together, the results of the present study suggest miR-15a induces ferroptosis by regulating GPX4 in prostate cancer cells, which provides evidence for investigating the therapeutic strategies of prostate cancer. MicroRNA-15a promotes prostate cancer cell ferroptosis by inhibiting GPX4 expression 2022 35069876 mmu-miR-214-3p MIMAT0000661 miRNA - mouse Acute kidney injury TCMK-1 CCK-8 assay ferrostatin-1 GPX4 GPX4 miR-214-3p would alleviate TEC ferroptosis in cis-AKI via GPX4 The relationship between TEC ferroptosis and cisplatin-induced AKI was investigated in vitro and in vivo. Ferrostatin-1(Fer-1), an inhibitor of ferroptosis, was observed to confer a protective effect against the renal tubular injury and renal failure induced by cisplatin. MicroRNAs (miRNAs) regulate the genes that have important functions in the development of cis-AKI. In the present study, GPX4 was predicted as a target of miR-214-3p. Moreover, inhibiting miR-214-3p enhanced the expressions of GPX4 and SLC7A11 while decreasing the ACSL4 expression. Furthermore, miR-214-3p down-regulation protected against TEC death and renal tubule damage both in vitro and in vivo. MicroRNA-214-3p aggravates ferroptosis by targeting GPX4 in cisplatin-induced acute kidney injury 2022 35366755 HULC ENSG00000285219 lncRNA - Homo sapiens (human) Hepatocellular carcinoma SMMC-7721 and BEL-7402 ROS Assay Kit - ATF4 ROS Downregulation of HULC induces ferroptosis HULC was found to function as a ceRNA of miR-3200-5p, and miR-3200-5p regulates ferroptosis by targeting ATF4, resulting in the inhibition of proliferation and metastasis within HCC cells. In summary, these findings illuminate some of the molecular mechanisms through which downregulation of HULC induces liver cancer cell ferroptosis by targeting the miR-3200-5p/ATF4 axis to modulate the development of hepatocellular carcinoma. Downregulation of HULC Induces Ferroptosis in Hepatocellular Carcinoma via Targeting of the miR-3200-5p/ATF4 Axis 2022 35615577 CircCDK14 hsa_circ_0001721 circRNA cytoplasm Homo sapiens (human) Glioma Brain CCK-8 assay erastin miR-3938/PDGFRA ROS CircCDK14 Promotes Tumor Progression and Resists Ferroptosis Transmission electron microscopic observation of mitochondria, iron and reactive oxygen species assays were employed for the detection of circCDK14 effect on glioma cells' sensitivity to erastin-induced ferroptosis (Fp). Our findings indicated that circCDK14 was overexpressed in glioma tissues and cell lines, and elevated levels of circCDK14 induced poor prognosis of glioma patients. CircCDK14 Promotes Tumor Progression and Resists Ferroptosis in Glioma by Regulating PDGFRA 2022 35002529 hsa-miR-21-3p MIMAT0004494 miRNA - Homo sapiens (human) Melanoma WM793B, A2058, A375, Hs294T CCK-8 assay erastin TXNRD1 ROS MiR-21-3p upregulation contributes to IFN-γ-driven ferroptosis MiRNAs expression profile of melanoma cells in IFN-γ-driven ferroptosis was first obtained. Then, upregulated miR-21-3p was proved to facilitate IFN-γ-mediated ferroptosis by potentiating lipid peroxidation. miR-21-3p increased the ferroptosis sensitivity by directly targeting thioredoxin reductase 1 (TXNRD1) to enhance lipid reactive oxygen species (ROS) generation. Furthermore, miR-21-3p overexpression in tumor synergized with anti-PD-1 antibody by promoting tumor cell ferroptosis. More importantly, miR-21-3p-loaded gold nanoparticles were constructed, and the systemic delivery of them increased the efficacy of anti-PD-1 antibody without prominent side effects in preclinical mice model. Ultimately, ATF3 was found to promote miR-21-3p transcription in IFN-γ-driven ferroptosis. Nanoparticle delivery of miR-21-3p sensitizes melanoma to anti-PD-1 immunotherapy by promoting ferroptosis 2022 35738798 hsa-miR-222 MI0000299 miRNA exosome Homo sapiens (human) Hepatitis B virus (HBV)-infected hepatocytes Liver CCK-8 assay - TFRC ROS Exosomal miR-222 derived from HBV-infected hepatocytes promoted LX-2 cell activation through suppressing TFRC-induced ferroptosis. The results showed that supplementation of exosomes derived from HBV-infected LO2 cells remarkably enhanced LX-2 cell activation, evidenced by elevated hydroxyprolin (Hyp) secretion and α-SMA and COL1A2 expression. miR-222 was significantly increased in HBV-Exo. Overexpressing miR-222 upregulated cell viability, secretion of Hpy, and expression of α-SMA and COL1A2, which were all blocked by overexpression of TFRC. Further study showed that TFRC was a target of miR-222, and miR-222 promoted LX-2 cell activation through suppressing TFRC-induced ferroptosis in LX-2 cells. Exosomal miR-222 derived from HBV-infected hepatocytes promoted LF through inhibiting TFRC and TFRC-induced ferroptosis. Exosomes derived from hepatitis B virus-infected hepatocytes promote liver fibrosis via miR-222/TFRC axis 2022 34978008 CircBCAR3 hsa_circ_0007624 circRNA cytoplasm Homo sapiens (human) Esophageal cancer Esophageal/EC109 CCK-8 assay - miR-27a-3p/TNPO1 ROS CircBCAR3 promoted the proliferation, migration, invasion, and ferroptosis We further demonstrated that circular RNA circBCAR3 was upregulated in the esophageal cancer tissues and cells and regulated the proliferation, migration, invasion, and ferroptosis of esophageal cancer cells in vitro. CircBCAR3 expression was increased by hypoxia and rescued the effects of hypoxia on esophageal cancer cells. Silenced circBCAR3 inhibited the esophageal cancer tumor growth and metastasis in vivo. Mechanistically, E2F7-induced splicing factor QKI increased circBCAR3. CircBCAR3 accelerates esophageal cancer tumorigenesis and metastasis via sponging miR-27a-3p 2022 35840974 rno-miR-672-3p MIMAT0017312 miRNA - rat Spinal cord injury AGE1.HN and PC12 CCK-8 assay erastin FSP1 ROS The miR-672-3p mimics promoted ferroptosis after SCI The luciferase reporter assay demonstrated that miR-672-3p downregulated FSP1, a glutathione-independent ferroptosis suppressor, by binding to its 3' untranslated region. Oxygen and glucose deprivation- (OGD-) treated PC12 and AGE1.HN cells were treated with miR-672-3p mimics or inhibitors in vitro. The effect of miR-672-3p mimics or inhibitor on OGD-PC12/AGE1.HN ferroptosis was evaluated by flow cytometry, immunohistochemistry, immunofluorescence, and western blotting. The miR-672-3p mimics promoted ferroptosis after SCI, whereas the miR-672-3p inhibitor inhibited this process. miR-672-3p Promotes Functional Recovery in Rats with Contusive Spinal Cord Injury by Inhibiting Ferroptosis Suppressor Protein 1 2022 35237382 hsa-miR-30e-5p MIMAT0000692 miRNA - Homo sapiens (human) Endothelial injury Endothelial progenitor cells (EPCs) MTT assay erastin SP1 ROS EPCs-Exos inhibited Erastin-induced HUVEC ferroptosis by upregulating miR-30e-5p EPCs-Exos inhibited Erastin-induced HUVEC ferroptosis and endothelial injury. Erastin inhibited miR-30e-5p and EPCs-Exo treatment recovered miR-30e-5p expression. miR-30e-5p was encapsulated in EPCs-Exos. After inhibiting miR-30e-5p in EPCs, the inhibitory effect of EPCs-Exos on HUVEC ferroptosis was attenuated. miR-30e-5p targeted SP1. Overexpression of SP1 partially reversed the effect of EPCs-Exos on improving HUVEC ferroptosis and increasing phosphorylation levels of AMPK. Collectively, EPCs-Exos inhibited Erastin-induced HUVEC ferroptosis by upregulating miR-30e-5p, inhibiting SP1, and activating the AMPK pathway. Endothelial progenitor cells-derived exosomes transfer microRNA-30e-5p to regulate Erastin-induced ferroptosis in human umbilical vein endothelial cells via the specificity protein 1/adenosine monophosphate-activated protein kinase axis 2022 35068337 hsa-miR-545-5p MIMAT0004785 miRNA - Homo sapiens (human) Colorectal cancer HT-29 and HCT-116 CCK-8 assay erastin TF ROS miR-545 suppresses ferroptosis via TF Our results demonstrate that miR-545 overexpression inhibited, while miR-545 knockdown further increased, erastin and RSL3-induced upregulation of MDA, reactive oxygen species (ROS), and Fe2+ levels. Similarly, miR-545 overexpression partially reversed, while miR-545 knockdown enhanced, the erastin and RSL3-induced reduction in HT-29 and HCT-116 cell survival rates. Transferrin (TF) was identified as a target gene of miR-545. To determine whether miR-545 suppresses ferroptosis via TF, we overexpressed TF in HT-29 and HCT-116 cells. We found that TF overexpression blocked miR-545-induced changes in ROS, MDA, and Fe2+ levels in HT-29 and HCT-116 cells, thereby inducing CRC cell death. miR-545 promotes colorectal cancer by inhibiting transferring in the non-normal ferroptosis signaling 2021 34954694 circ-PSEN1 - circRNA - Homo sapiens (human) Diabetic retinopathy ARPE19 MTT assay - miR-200b-3p/CFL2 GSH Knockdown of circ-PSEN1 can mitigate ferroptosis circ-PSEN1 was upregulated in HG-treated ARPE19 cells and showed high resistance to RNase R and Act D. Inhibition of circ-PSEN1 in ARPE19 cells ameliorated the ferroptosis induced by HG was ameliorated, as evidenced by changes in the ferroptosis-related biomarkers/genes and decreased cell death. Subsequently, circ-PSEN1 acted as a sponge for miR-200b-3p. Inhibition of miR-200b-3p partially reversed the effects of circ-PSEN1 on ferroptosis. Furthermore, cofilin-2 (CFL2) was the target gene of miR-200b-3p, and it abrogated the inhibitory effect of miR-200b-3p on ferroptosis. Taken together, the findings indicate that knockdown of circ-PSEN1 can mitigate ferroptosis of ARPE19 cells induced by HG via the miR-200b-3p/CFL2 axis. Downregulation of Circular RNA PSEN1 ameliorates ferroptosis of the high glucose treated retinal pigment epithelial cells via miR-200b-3p/cofilin-2 axis 2021 34903141 ADAMTS9-AS1 ENSG00000241158 lncRNA cytoplasm Homo sapiens (human) Endometriosis Endometrial tissues CCK-8 assay erastin miR-6516-5p/GPX4 GSH and ROS Upregulated ADAMTS9-AS1 accelerates ESC proliferation and migration by regulating miR-6516-5p/GPX4-dependent ferroptosis The regulatory role of ADAMTS9-AS1 in ferroptosis was defined and evidenced by increased reactive oxygen species (ROS) levels and malonyl dialdehyde (MDA) content and decreased expression of glutathione peroxidase 4 (GPX4) after ADAMTS9-AS1 inhibition. Mechanistically, ADAMTS9-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-6516-5p to derepress the expression of GPX4, the critical repressor of ferroptosis. Long noncoding RNA ADAMTS9-AS1 represses ferroptosis of endometrial stromal cells by regulating the miR-6516-5p/GPX4 axis in endometriosis 2022 35173188 rno-miR-29a-3p MIMAT0000802 miRNA exosome rat Hepatic ischemia-reperfusion injury Bone marrow mesenchymal stem cells CCK-8 assay ferrostatin-1 Ireb2 ROS Overexpression of miR-29a-3p downregulated the expression of Ireb2 and inhibited ferroptosis We confirmed high levels of miR-29a-3p in HO-1/BMMSCs exosomes. Overexpression of miR-29a-3p downregulated the expression of Ireb2 and inhibited ferroptosis. Downregulation of miR-29a-3p blocked the protective effect of HO-1/BMMSC exosomes on SHP-HR cell injury. In conclusion, ferroptosis plays an important role in HO-1/BMMSC-mediated alleviation of steatotic liver IRI. HO-1/BMMSCs could suppress ferroptosis by targeting Ireb2 via the exosomal transfer of miR-29a-3p. miR-29a-3p in Exosomes from Heme Oxygenase-1 Modified Bone Marrow Mesenchymal Stem Cells Alleviates Steatotic Liver Ischemia-Reperfusion Injury in Rats by Suppressing Ferroptosis via Iron Responsive Element Binding Protein 2 2022 35720183 lncGm36569 - lncRNA exosome rat Acute spinal cord injury HT-22 and HEK-293 T CCK-8 assay - miR-5627-5p/FSP1 ROS lncGm36569 inhibited neuronal cell ferroptosis Further study demonstrated that lncGm36569 was enriched in the MSCs-exo. Through bioinformatics analysis and luciferase assay, we confirmed that lncGm36569 acted as a competitive RNA of miR-5627-5p to induce FSP1 upregulation. Furthermore, overexpression of miR-5627-5p reversed the therapeutic effects of lncGm36569 on neuronal cell ferroptosis. In conclusion, MSCs-exosomes lncGm36569 inhibited neuronal cell ferroptosis through miR-5627-5p/FSP1 axis, thereby attenuating neuronal dysfunction. Mesenchymal Stem Cell Derived Exosomes Suppress Neuronal Cell Ferroptosis Via lncGm36569/miR-5627-5p/FSP1 Axis in Acute Spinal Cord Injury 2022 35257299 hsa-miR-27a-3p MIMAT0000084 miRNA - rat Ischaemic stroke Brain GSH assay kit ferrostatin-1 Nrf2 GPX4 and GSH miRNA‑27a may aggravate brain tissue ferroptosis during ischaemic stroke These results indicated that ferroptosis intensified over time during IS. In addition, the miRNA‑27a agonist significantly aggravated ferroptosis and reduced neurological function scores compared with those of the control group. Subsequently, a luciferase reporter gene system verified the targeted binding of miRNA‑27a to Nrf2. The results showed that miRNA‑27a inhibited Nrf2 in a targeted manner, which also exacerbated the extent of ferroptosis. However, the miRNA‑27a antagonist reversed the miR‑27a agonist‑mediated effects. Therefore, the present study indicated that miRNA‑27a may aggravate brain tissue ferroptosis during ischaemic stroke, potentially by inhibiting Nrf2. Micro Ribonucleic Acid 27a Aggravates Ferroptosis During Early Ischemic Stroke of Rats Through Nuclear Factor Erythroid-2-Related Factor 2 2022 36180007 hsa-miR-2115-3p MIMAT0011159 miRNA - rat Preeclampsia Umbilical cord blood and placenta CCK-8 assay ferrostatin-1 GOT1 GSH miR-2115-3p inhibits ferroptosis In vivo, ferrostatin-1 attenuated ferroptosis in the PE models, significantly increasing fetal survivability. The miR-2115-3p/GOT1 pathway was screened for possible association with abnormal ferroptosis in PE. miR-2115-3p was discovered to interact with the mRNA of GOT1. Inhibition of GOT1 and overexpression of miR-2115-3p reversed the decrease in cell proliferation capacity, GSH, GSH-PX, and GPX4 levels, and the increase in ROS, ACSL4, TfR1, MDA, total Fe, and Fe (II) levels induced by hypoxia. However, simultaneous overexpression of miR-2115-3p and GOT1 reversed the above results of overexpression of miR-2115-3p. miR-2115-3p inhibits ferroptosis by downregulating the expression of glutamic-oxaloacetic transaminase in preeclampsia 2022 36279730 LINC01606 ENSG00000253301 lncRNA cytoplasm Homo sapiens (human) Colon cancer SW480 and HT29 CCK-8 assay ferrostatin‐1 (Fer‐1), Erastin miR-423-5p/Wnt/β‐catenin ROS LINC01606 protects colon cancer cells from ferroptotic cell death The expression of lncRNA LINC01606 was frequently upregulated in human colon cancer and strongly associated with a poor prognosis. LINC01606 functioned as an oncogene and promotes colon cancer cell growth, invasion and stemness both in vitro and in vivo. Moreover, LINC01606 protected colon cancer cells from ferroptosis by decreasing the concentration of iron, lipid reactive oxygen species, mitochondrial superoxide and increasing mitochondrial membrane potential. Mechanistically, LINC01606 enhanced the expression of stearoyl‐CoA desaturase 1 (SCD1), serving as a competing endogenous RNA to modulate miR‐423‐5p expression, subsequently activating the canonical Wnt/β‐catenin signaling, and transcription factor binding to IGHM enhancer 3 (TFE3) increased LINC01606 transcription after recruitment to the promoter regions of LINC01606. Furthermore, we confirmed that upregulated LINC01606 and Wnt/β‐catenin formed a positive feedback regulatory loop, further inhibiting ferroptosis and enhancing stemness. Long noncoding RNA LINC01606 protects colon cancer cells from ferroptotic cell death and promotes stemness by SCD1-Wnt/β-catenin-TFE3 feedback loop signalling 2022 35485210 hsa-miR-138-5p MIMAT0000430 miRNA nucleus Homo sapiens (human) Diabetic retinopathy ARPE-19 cells calcein+ ferrostatin-1 Sirt1/Nrf2 GSH AS-IV inhibited miR-138-5p expression, subsequently increasing Sirt1/Nrf2 activity and cellular antioxidant capacity to alleviate ferroptosis In addition, AS-IV could inhibit miR-138-5p expression, increase Sirt1/Nrf2 activity, and enhance cellular antioxidant capacity by antagonizing ferroptosis-related processes, thus reducing death of RPE cells. The results of the present study contribute to the understanding of the mechanism underlying high glucose-induced cell apoptosis, and indicate that AS-IV holds potential therapeutic value for DR. Astragaloside-IV alleviates high glucose-induced ferroptosis in retinal pigment epithelial cells by disrupting the expression of miR-138-5p/Sirt1/Nrf2 2022 35302431 hsa-miR-93-5p MIMAT0000093 miRNA - Homo sapiens (human) Polycystic ovary syndrome KGN cells CCK-8 assay erastin TLR4 ROS miR-93-5p promotes the apoptosis and ferroptosis in GC miR-93-5p was upregulated in the GCs of PCOS patients. Overexpression of miR-93-5p promoted apoptosis and ferroptosis in KGN cells, while knockdown of miR-93-5p showed the reverse effect. Biological analysis and subsequent experiments demonstrated that miR-93-5p negatively regulates the NF- κB signaling pathway. MiR-93-5p promotes granulosa cell apoptosis and ferroptosis by the NF-kB signaling pathway in polycystic ovary syndrome 2022 36341347 mmu-miR-149 MI0000171 miRNA - mouse Endotoxemia Ventricular tissues CCK-8 assay ferrostatin-1 HMGB1 ROS Resveratrol upregulated miR-149 and downregulated HMGB1 to inhibit ferroptosis Resveratrol improved LPS-induced endotoxemia cardiomyocyte injury by upregulating miR-149 and inhibiting ferroptosis. Resveratrol inhibited HMGB1 expression by upregulating miR-149. HMGB1 upregulation reversed the inhibitory effect of miR-149 on LPS-induced ferroptosis in cardiomyocytes. Resveratrol upregulated miR-149 and downregulated HMGB1 to inhibit ferroptosis and improve myocardial injury in mice with LPS-induced endotoxemia. Collectively, resveratrol upregulated miR-149, downregulated HMGB1, and inhibited the ferroptosis pathway, thus improving cardiomyocyte injury in LPS-induced endotoxemia. Resveratrol mediates the miR-149/HMGB1 axis and regulates the ferroptosis pathway to protect myocardium in endotoxemia mice 2022 35532075 hsa-miR-142-3p MIMAT0000434 miRNA exosome Homo sapiens (human) Hepatocellular carcinoma HepG2 and THP-1 TBARS assay kit - SLC3A2 GSH and ROS miR-142-3p promoted HBV-infected M1-type macrophage ferroptosis MiR-142-3p was highly expressed in HBV-infected HCC patients and HBV-infected M1-type macrophages. Inhibition of miR-142-3p or overexpression of SLC3A2 reversed ferroptosis and inhibited the proliferation, migration, and invasion of HCC cells. Exosomal miR-142-3p secreted by hepatitis B virus (HBV)-hepatocellular carcinoma (HCC) cells promotes ferroptosis of M1-type macrophages through SLC3A2 and the mechanism of HCC progression 2022 35557596 hsa-miR-19a MI0000073 miRNA - Homo sapiens (human) Colorectal cancer HT29 CCK-8 assay - IREB2 ROS ferroptosis was suppressed by miR-19a through inhibiting IREB2 Studies have shown that miR-19a is identified as oncogenic miRNA and promotes the proliferation, migration and invasion of CRC cells. However, the relationship between miR-19a and ferroptosis in CRC remains unknown. Here, we reported that iron-responsive element-binding protein 2 (IREB2), as an inducer of ferroptosis, was negatively regulated by miR-19a. IREB2 is a direct target of miR-19a. In addition, ferroptosis was suppressed by miR-19a through inhibiting IREB2. Thus, we proposed a novel mechanism of ferroptosis mediated by miR-19a in CRC cells, which could give rise to a new strategy for the therapy of CRC. MiR-19a suppresses ferroptosis of colorectal cancer cells by targeting IREB2 2022 35599631 circ_0072464 hsa_circ_0072464 circRNA - mice Intervertebral disc degeneration Bone marrow tissues CCK-8 assay erastin miR-431/NRF2 ROS circ_0072464 inhibited NPC ferroptosis circ_0072464 and NRF2 were downregulated, and miR-431 was upregulated in IDD. Mechanistically, circ_0072464 competitively bound to miR-431, which targeted and inhibited NRF2 expression. BMSC-derived EVs carrying circ_0072464 inhibited NPC ferroptosis to promote matrix synthesis and proliferation of NPCs by inhibiting miR-431 and upregulating NRF2. Besides, in vivo experiments also confirmed that BMSC-EVs alleviated intervertebral disc lesions in mice with IDD through the circ_0072464/miR-431/NRF2 axis. Collectively, BMSC-EV-loaded circ_0072464 inhibited NPC ferroptosis to relieve IDD via upregulation of miR-431-mediated NRF2, therefore providing a potential therapeutic target against IDD. circ_0072464 Shuttled by Bone Mesenchymal Stem Cell-Secreted Extracellular Vesicles Inhibits Nucleus Pulposus Cell Ferroptosis to Relieve Intervertebral Disc Degeneration 2022 35814268 gga-miR-129-3p MIMAT0050082 miRNA - Broilers - Liver tissues CCK-8 assay erastin SLC7A11 GSH and ROS miR-129-3p regulated the GCL/GSS/GPX4 axis by targeting SLC7A11, resulting in an increase in ROS to induce ferroptosis The results showed that the expression level of miR-129-3p mRNA in Se-deficient liver was significantly increased. To understand whether the miR-129-3p/SLC7A11 axis could involve in the process of ferroptosis, our further research showed that overexpression of miR-129-3p could reduce the expression of SLC7A11 and its downstream GCL, GSS, and GPX4, thereby inducing ferroptosis. These data indicates that miR-129-3p affected ferroptosis under Se deficiency conditions through the SLC7A11 pathway. MiR-129-3p regulates ferroptosis in the liver of Selenium-deficient broilers by targeting SLC7A11 2023 36436380 hsa-miR-147a MIMAT0000251 miRNA - Homo sapiens (human) Glioblastoma U87MG, A172, HA1800, and SVGp12 CCK-8 assay erastin SLC40A1 GPX4 and GSH miR-147a targets SLC40A1 to induce ferroptosis Treatment with the miR-147a mimic significantly induced ferroptosis of glioblastoma cells, and the ferroptotic inhibitors could block the miR-147a mimic-mediated tumor suppression in vitro. Conversely, the miR-147a inhibitor prevented erastin- or RSL3-induced ferroptosis and increased the viability of glioblastoma cells in vitro. Mechanistically, we determined that miR-147a directly bound to the 3'-untranslated region of SLC40A1 and inhibited SLC40A1-mediated iron export, thereby facilitating iron overload, lipid peroxidation, and ferroptosis. MicroRNA-147a Targets SLC40A1 to Induce Ferroptosis in Human Glioblastoma 2022 35942174 Circ_0000745 hsa_circ_0000745 circRNA cytoplasm Homo sapiens (human) Acute lymphoblastic leukemia Kasumi-1 and KG-1 MTT assay ferrostatin-1 miR-494-3p/NET1 ROS Circ_0000745 contributed to ALL development partly by binding to miR-494-3p to induce NET1 expression.0020 Circ_0000745 expression was elevated in ALL patients and cell lines. Circ_0000745 knockdown restrained cell cycle progression and glycolysis and triggered cell apoptosis and ferroptosis. Circ_0000745 acted as a molecular sponge for miR-494-3p in ALL cells. miR-494-3p silencing partly diminished circ_0000745 knockdown-induced anti-tumor effects in ALL cells. NET1 was a target of miR-494-3p, and miR-494-3p overexpression-induced anti-tumor influences were partly counteracted by the accumulation of NET1 in ALL cells. Circ_0000745 can positively regulate NET1 expression by sponging miR-494-3p in ALL cells. Circ_0000745 promotes acute lymphoblastic leukemia progression through mediating miR-494-3p/NET1 axis 2022 34957935 circFOXP1 hsa_circ_0066527 circRNA cytoplasm Homo sapiens (human) Lung cancer Lung cancer tissues CCK-8 assay - miR-520a-5p/SLC7A11 ROS circFOXP1 shRNA-induced ferroptosis The expression of E-cadherin was enhanced, and vimentin expression was reduced by the knockdown of circFOXP1. Moreover, the treatment of ferroptosis activator erastin or RSL3 repressed the cell viability of lung cancer cells and the overexpression of circFOXP1 rescued the phenotype. The levels of malondialdehyde (MDA), iron, and lipid reactive oxygen species (ROS) were enhanced by the silencing of circFOXP1 in both erastin and RSL3-stimulated lung cancer cells. Mechanically, circFOXP1 increased SLC7A11 expression by directly sponging miR-520a-5p in lung cancer cells. The inhibitor of miR-520a-5p or the overexpression of SLC7A11 reversed circFOXP1 shRNA-induced ferroptosis phenotypes in lung cancer cells. Importantly, circFOXP1 contributed to tumor growth of lung cancer cells by enhancing SLC7A11 in vivo. Potential of Curcumin and Quercetin in Modulation of Premature Mitochondrial Senescence and Related Changes during Lung Carcinogenesis 2021 34936300 hsa-miR-378a-3p MIMAT0000732 miRNA - Homo sapiens (human) Nerve injury HT22 cells CCK-8 assay ferrostatin-1 SLC7A11 GSH and ROS Inhibition of miR-378a-3p enhanced the mRNA expression of SLC7A11 and attenuated Pb-induced ferroptosis in vitro Overexpression of SLC7A11 reversed the changes in MDA and GSH levels and cell viability induced by lead exposure. In contrast, lower expression of SLC7A11 accelerated the changes in these parameters. Consequently, we screened miRNAs that regulate SLC7A11 using TargetScan. We found that miR-378a-3p showed the highest expression among the target miRNAs regulating SLC7A11 expression. Inhibition of miR-378a-3p expression reversed the reduction in GSH and the increase in lipid ROS levels induced by lead exposure. Taken together, these findings indicate that lead exposure can cause ferroptosis and that miR-378a-3p exerted an important effect by regulating SLC7A11 expression. MiR-378a-3p/ SLC7A11 regulate ferroptosis in nerve injury induced by lead exposure 2022 35588615 SLC16A1-AS1 ENSG00000226419 lncRNA cytoplasm Homo sapiens (human) Renal cell carcinoma HK-2 cells CCK-8 assay - miR-143-3p/SLC7A11 GPX4 Silencing lncRNA SLC16A1-AS1 can induce ferroptosis Our study revealed that SLC16A1-AS1 has high expression and was associated with overall survival in renal cancer. Knockdown SLC16A1-AS1 inhibited cell viability, proliferation, and migration of renal cancer cells. Furthermore, it was demonstrated that SLC16A1-AS1 served as a sponge of miR-143-3p, and knockdown SLC16A1-AS1 significantly increased the enrichment of miR-143-3p. And then, SLC7A11 was identified as the target protein of miR-143-3p, and overexpression miR-143-3p remarkably inhibited the expression of SLC7A11. Moreover, knockdown SLC16A1-AS1 could aggravate this effect. Finally, through inhibiting SLC7A11 expression, silencing SLC16A1-AS1 induced ferroptosis via increasing miR-143-3p. Silencing lncRNA SLC16A1-AS1 Induced Ferroptosis in Renal Cell Carcinoma Through miR-143-3p/SLC7A11 Signaling 2022 35167383 NEAT1 ENSG00000245532 lncRNA nucleus Homo sapiens (human) Parkinson's disease SK‑N‑SH cells MTT assay - miR‑150‑5p/BAP1 ROS LncRNA NEAT1 promoted MPP+‑induced ferroptosis Knockdown of NEAT1 elevated viability and GSH level in PD cell model and reduced ROS, MDA, and Fe2+ levels. Moreover, NEAT1 functioned as a sponge to suppress miR‑150‑5p expression. Moreover, miR‑150‑5p overexpression suppressed ferroptosis in PD cell model. We subsequently found that miR‑150‑5p regulated SLC7A11 expression by directly binding to BAP1. miR‑150‑5p inhibition or BAP1 overexpression mitigated the anti‑ferroptosis effect meditated by sh‑NEAT1. Taken together, knockdown of NEAT1 mitigated MPP+‑induced ferroptosis through regulating BAP1/SLC7A11 axis by sponging miR‑150‑5p, indicating the potential of NEAT1 as a promising therapeutic target for PD. LncRNA NEAT1 promoted MPP+‑induced ferroptosis via regulating miR‑150‑5p/BAP1 pathway in SK‑N‑SH cells 2022 35833822 Gm47283 ENSMUSG00000096768 lncRNA - mice Myocardial infarction HL-1 cell line fluorescence microscope - miR-706/ Ptgs2 ROS Inhibition or overexpression of lncRNA Gm47283 could regulate Ptgs2 expression and downstream ferroptosis activity Mechanically, co-transfection experiments showed that overexpression of miR-706 could reverse the damage effect that was caused by lncRNA Gm47283 overexpression, via inhibiting Ptgs2 and ferroptosis. Additionally, inhibition of lncRNA Gm47283 by stem cell membrane coated siRNA could attenuate MI in vivo. Our study elucidated a novel mechanism containing lncRNA Gm47283/miR-706/Ptgs2/ferroptosis in MI, which provided a potential therapeutic for MI.Graphical Abstract. Stem cell membrane coated siRNA of lncRNA Gm47283 inhibits cardiomyocyte ferroptosis in myocardial infarction rat. Stem cell membrane-coated siRNA of lncRNA Gm47283 increases miR-706, and then miR-706 suppresses the expression of Ptgs2 to reduce lipid peroxidation toxicity, and then inhibits cardiomyocyte ferroptosis. Suppression of lncRNA Gm47283 attenuates myocardial infarction via miR-706/ Ptgs2/ferroptosis axis 2022 35485136 mmu-miR-7212-5p MIMAT0028392 miRNA - mice Sepsis-associated acute kidney injury Kidney tissue Western blotting - Hmox1 ROS Inhibitor of mmu-miR-7212-5p attenuates ferroptosis A total of 4,754 DEGs were identified between the two groups using high-throughput sequencing. The pathways in which DEGs were enriched included ferroptosis (the highest enrichment score), apoptosis, and the PI3K-Akt, NF-kappa B and IL-17 signaling pathways. Seven (Hmox1, Spp1, Socs3, Mapk14, Lcn2, Cxcl1 and Cxcl12) of the 15 hub genes were involved in the KEGG pathway. mmu-miR-7212-5p-Hmox1 was a key RNA regulatory axis in ferroptosis. m6A RNA methylation modifications were involved in SA-AKI. The correlation analyses showed the close interactions among the m6A RNA methylation regulators and important hub genes. 2022 35957725 ZFAS1 ENSG00000177410 lncRNA cytoplasm Homo sapiens (human) Diabetic retinopathy hRECs Western blotting ferrostatin-1 miR-7-5p/ACSL4 GPX4 HG-induced ZFAS1 elevation activates ferroptosis We validated that ZFAS1 may act as a competing endogenous RNA by competitively binding with microRNA-7-5p (miR-7-5p) and modulating the expression of its downstream molecule acyl-CoA synthetase long-chain family member 4 (ACSL4), which is now identified as a classic driver gene of ferroptosis process. In conclusion, our results demonstrate that HG-induced ZFAS1 elevation activates ferroptosis in hRECs and the ZFAS1/miR-7-5p/ACSL4 axis may serve as a therapeutic target for endothelial dysfunction in DR. lncRNA ZFAS1 Positively Facilitates Endothelial Ferroptosis via miR-7-5p/ACSL4 Axis in Diabetic Retinopathy 2022 36092160 hsa-miR-324-3p MIMAT0000762 miRNA - Homo sapiens (human) Renal cell carcinoma ACHN, A498, 786-O, Caki-1 CCK-8 assay ferrostatin-1 GPX4 GPX4 ICS II-induced ferroptosis via the miR-324-3p/GPX4 axis in RCC cells The underlying mechanism was found to be the downregulation of GPX4, independent of p53, that occurs during ICS II-induced ferroptosis. Overexpression of GPX4 reversed the ferroptosis induced by ICS II. Moreover, ICS II treatment resulted in the upregulation of miR-324-3p, which directly targets GPX4. Overall, our results suggested that ICS II-induced ferroptosis via the miR-324-3p/GPX4 axis in RCC cells could be a promising therapeutic agent for RCC. Icariside II induces ferroptosis in renal cell carcinoma cells by regulating the miR-324-3p/GPX4 axis 2022 35636172 rno-miR-199a-5p MIMAT0000872 miRNA - rat Myocardial ischemia/reperfusion H9c2 CCK-8 assay ferrostatin-1 Akt/eNOS Gpx4 miR-199a-5 promotes ferroptosis-induced cardiomyocyte death MiR-199a-5p inhibitor ameliorated ferroptosis-induced cardiomyocyte death as evidenced by the increased cell viability, the reduced reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) and Fe2+ contents, and the up-regulated glutathione (GSH)/glutathione disulphide (GSSG) ratio as well as glutathione peroxidase 4 (Gpx4) protein expression in H9c2 cells-exposed to OGD/R, while miR-199a-5p mimic had the opposite effects. In addition, OGD/R led to the inhibition of Akt/eNOS signaling pathway, which was also blocked by miR-199a-5p inhibitor and aggravated by miR-199a-5p mimic. Furthermore, LY294002, an inhibitor of Akt/eNOS signaling pathway, abrogated miR-199a-5p inhibitor-induced the reduction of ferroptosis-induced cardiomyocyte death. MiR-199a-5p promotes ferroptosis-induced cardiomyocyte death responding to oxygen-glucose deprivation/reperfusion injury via inhibiting Akt/eNOS signaling pathway 2022 36254861 hsa-miR-34c-3p MIMAT0004677 miRNA - Homo sapiens (human) Oral squamous cell carcinoma Oral squamous cell carcinoma tissues CCK-8 assay erastin SLC7A11 ROS miR-34c-3p promoted ferroptosis by increasing ROS The results showed lower expression of miR-34c-3p in OSSC compared with normal tissues. Overexpression of miR-34c-3p in SCC-25 cells suppressed cell proliferation. In addition, the overexpression of miR-34c-3p promoted ferroptosis by increasing ROS, MDA, and iron and decreasing GSH and GPX4 levels in SCC-25 cells. MiR-34c-3p upregulates erastin-induced ferroptosis to inhibit proliferation in oral squamous cell carcinomas by targeting SLC7A11 2022 35093695 rno-miR-375-3p MIMAT0005307 miRNA - rat Cardiac fibrosis Heart tissue CCK-8 assay ferrostatin-1 GPX4 GPX4 MiR-375-3p is an important factor inducing myocardial fibrosis after MI, which accelerates the ferroptosis of cardiomyocytes In the I/R rat model and CF cell model, miR-375-3p promoted fibrosis by accelerating the ferroptosis of cardiomyocytes through mediating glutathione peroxidase 4 (GPX4). Furthermore, we treated the rats or cell model with miR-375-3p antagomir (or inhibitor) and ferroptosis inhibitor Ferrostatin-1 (Fer-1). The results showed that miR-375-3p antagomir (or inhibitor) and Fer-1 promoted the antioxidant capacity of cardiac fibroblasts, reduced GPX4-mediated ferroptosis process and alleviated I/R-induced CF. MiR-375-3p Promotes Cardiac Fibrosis by Regulating the Ferroptosis Mediated by GPX4 2022 35498204 hsa-miR-4735-3p MIMAT0019861 miRNA - Homo sapiens (human) Clear cell renal cell carcinoma 796-O and A498 MTT method ferrostatin-1 SLC40A1 ROS miR-4735-3p facilitates ferroptosis miR-4735-3p expression was reduced in human ccRCC tissues and cell lines but elevated upon ferroptotic stimulation. The miR-4735-3p mimic increased, while the miR-4735-3p inhibitor decreased oxidative stress, lipid peroxidation, iron overload, and ferroptosis of human ccRCC cell lines. Mechanistic studies identified SLC40A1 as a direct target of miR-4735-3p, and SLC40A1 overexpression significantly attenuated iron overload and ferroptosis in the miR-4735-3p mimic-treated human ccRCC cell lines. MicroRNA-4735-3p Facilitates Ferroptosis in Clear Cell Renal Cell Carcinoma by Targeting SLC40A1 2022 35646516 rno-miR-196c-3p MIMAT0017299 miRNA - rat Cardiac ischemia-reperfusion injury H9c2 CCK-8 assay - LOX, NOX4, and P53 ROS mir-196c-3p could simultaneously regulate the expression of ferroptosis-related genes LOX, NOX4, and P53 The mir-196c-3p mimic (mimics) and photothermal nanoparticles (BTN) were co-encapsulated in an injectable Gel (mimics + Gel/BTN) with NIR-II light-triggered release. Using 1064 nm light irradiation, local microenvironment photothermal-triggered on-demand noninvasive controllable delivery of miRNA was achieved, aiming to inhibit I/R-induced ferroptosis. Consequently, declined ferroptosis in cardiomyocytes and improved cardiac function, survival rate in rats was achieved through the controlled release of Gel/BTN mimics in I/R model to simultaneously inhibit ferroptosis hub genes NOX4, P53, and LOX expression. Delivery of Mir-196c-3p with NIR-II light-triggered gel attenuates cardiomyocyte ferroptosis in cardiac ischemia-reperfusion injury 2023 36270453 circAFF1 mmu_circ_0011938 circRNA - mouse Intracerebral hemorrhage brain tissues CCK-8 assay - miR-140-5p/GSK-3β ROS circAFF1 knockdown can suppress neuronal ferroptosis circAFF1 was highly expressed in ICH cell model. Knockdown of circAFF1 attenuated Hb-induced neuronal ferroptosis, as evidenced by inhibiting cell viability, ROS, MDA and iron ion, and promoting GDH levels, which can be counteracted by miR-140-5p knockdown. circAFF1 can target miR-140-5p, and GSK-3β was a target gene of miR-140-5p. The effect of miR-140-5p on neuronal ferroptosis can be reversed by GSK-3β overexpression. In vivo experiments identified knockdown of circAFF1 suppress ICH injury and inhibits neuronal ferroptosis through regulating miR-140-5p/GSK-3β axis. circAFF1 enhances intracerebral hemorrhage induced neuronal ferroptosis by targeting miR-140-5p to regulate GSK-3β mediated Wnt/β-catenin signal pathway 2022 35952845 Lnc-TC - lncRNA cytoplasm Homo sapiens (human) Benzene hematotoxicity AHH-1 MTT assay - miR-142-5p/CUL4B ROS Lnc-TC/miR-142-5p/CUL4B signaling axis promoted cell ferroptosis We observed that the expression of lncRNA TC (Lnc-TC) and CUL4B were increased, but miR-142-5p was decreased in benzene-exposed workers. Correlation analysis suggested that the ceRNAs had co-expression relationships, and were associated with blood cell counts. We further explored the role of ceRNA in vitro, and discovered that 1,4- benzoquinone (1,4-BQ) stimulated ferroptosis in AHH-1 cells by inhibiting the expression of GPX4 and SLC7A11, which was partially relieved by knockdown of Lnc-TC and CUL4B. Finally, by interfering with Lnc-TC and miR-142-5p expression, we confirmed that Lnc-TC acted as a microRNA sponge to reduce the accessibility and inhibition of miR-142-5p to CUL4B, thus increasing the expression of CUL4B. Lnc-TC/miR-142-5p/CUL4B signaling axis promoted cell ferroptosis to participate in benzene hematotoxicity 2022 36272464 LINC00551 ENSG00000272274 lncRNA - Homo sapiens (human) Lung adenocarcinoma PC9 and A549 CCK-8 assay RSL-3 miR-4328/DDIT4 ROS LINC00551 promotes autophagy-dependent ferroptosis This study characterized a long intergenic noncoding RNA, LINC00551, expressed at a low level in lung adenocarcinoma (LUAD) and some other cancers. Overexpression of LINC00551 suppresses cell viability while promoting autophagy and RSL-3-induced ferroptosis in LUAD cells. LINC00551 acts as a competing endogenous RNA (ceRNA) and binds with miR-4328 which up-regulates the target DNA damage-inducible transcript 4 (DDIT4). DDIT4 inhibits the activity of mTOR, promotes LUAD autophagy, and then promotes the ferroptosis of LUAD cells in an autophagy-dependent manner. Overexpression of LINC00551 promotes autophagy-dependent ferroptosis of lung adenocarcinoma via upregulating DDIT4 by sponging miR-4328 2022 36570007 hsa-miR-494-3p MIMAT0002816 miRNA - Homo sapiens (human) Parkinson's Disease LUHMES cells CCK-8 assay erastin SP1 and ACSL4 ROS miR-494-3p Promotes Erastin-Induced Ferroptosis Erastin could dose-dependently induce neuron injury and ferroptosis of LUHMES cells. miR-494-3p overexpression induced ROS production, mitochondrial damage, ferroptosis, and neuron injury in erastin-induced LUHMES cells. Likewise, miR-494-3p inhibition had the opposite effects. We also showed that REST was a target gene of miR-494-3p and could repress erastin-induced ferroptosis, neuron injury, ROS, and mitochondrial injury via SP1 in LUHMES cells. Moreover, we demonstrated that SP1 could interact with ACSL4. We also confirmed that miR-494-3p could aggravate the pathological changes of substantia nigra and corpus striatum in the MPTP-induced PD mouse model. miR-494-3p Promotes Erastin-Induced Ferroptosis by Targeting REST to Activate the Interplay between SP1 and ACSL4 in Parkinson's Disease 2022 35936219 LINC00616 ENSG00000248307 lncRNA - Homo sapiens (human) Chronic periodontitis Periodontal ligament stem cell MTT assay erastin miR-370/TFRC ROS LINC00616 acted as a competitive endogenous RNA (ceRNA) to promote ferroptosis The lncRNA LINC00616 was upregulated in periodontitis ligament tissues of patients with periodontitis and in PDLSCs treated with LPS-PG. Inhibition of LINC00616 promoted cell viability and suppressed ferroptosis of PDLSCs. miR-370 was verified to be a target of LINC00616, and suppressed miR-370 reversed the effects of LINC00616 knockdown on cell viability and ferroptosis in PDLSCs. Additionally, miR-370 targeting the transferrin receptor protein and upregulated transferrin receptor (TFRC) abolished the effects of overexpressed miR-370 on cell viability and ferroptosis of PDLSCs. LINC00616 acted as a competitive endogenous RNA (ceRNA) to promote ferroptosis of PDLSCs via the miR-370/TFRC axis. Therefore, LINC00616 knockdown may be a promising therapeutic strategy for periodontitis. Long non-coding RNA LINC00616 promotes ferroptosis of periodontal ligament stem cells via the microRNA-370 / transferrin receptor axis 2022 35611986 hsa-miR-1-3p MIMAT0000416 miRNA - Homo sapiens (human) Ovarian cancer HOSE CCK-8 assay erastin/RSL3 FZD7 MDA MiR-1-3p enhances the sensitivity of ovarian cancer cells to ferroptosis by targeting FZD7 MiR-1-3p enhances the sensitivity of ovarian cancer cells to ferroptosis by targeting FZD7 2022 36481629 hsa-miR-127-5p MIMAT0004604 miRNA - Homo sapiens (human) Meningiomas HMCs, HUM-iCell-n002, iCell CCK-8 assay - JAM3 ROS Elevated Expression of miR-127-5p Promoted Ferroptosis Expression levels of miR-127-5p and JAM3 were analyzed by RT-qPCR. GPX4 expression was quantified by western blotting. Results. miR-127-5p was expressed at low levels in IOMM-Lee cells, while JAM3 was highly expressed in IOMM-Lee cells. A dual luciferase assay demonstrated that miR-127-5p could target JAM3. Upregulation of miR-127-5p in IOMM-Lee cells resulted in cell cycle arrest and inhibition of cell activity. Upregulation of miR-127-5p increased LDH, MDA, and ROS levels and Fe2+ content and inhibited the expression of GPX4 protein. Upregulation of JAM3 reversed the results of miR-127-5p upregulation. Conclusion. miR-127-5p regulated meningioma formation and ferroptosis through JAM3, providing insights for the development of new treatments for meningioma. miR-127-5p Targets JAM3 to Regulate Ferroptosis, Proliferation, and Metastasis in Malignant Meningioma Cells 2022 35818586 hsa-miR-132 MI0000449 miRNA - Homo sapiens (human) Atherosclerosis HUVECs - - - ROS MiR-132 promotes atherosclerosis by inducing mitochondrial oxidative stress-mediated ferroptosis RT-qPCR results showed that miR-132 was significantly up-regulated in atherosclerotic plaques compared with normal vascular samples (P < 0.001). Compared with control HUVECs, HUVECs overexpressing miR-132 showed a significantly increased level of intracellular ROS (P < 0.001), and most of ROS was colocalized with mitochondria. HUVECs overexpressing miR-132 also showed significantly decreased MMP (P < 0.001) and obviously increased mtROS (P < 0.001) and opening of mPTP (P < 0.001), which led to mitochondrial REDOX respiratory chain stress disorder. The key iron death protein GPX4 was significantly down-regulated and the oxidized protein NOX4 was significantly increased in miR-132-overexpressing HUVECs. MicroRNA-132 promotes atherosclerosis by inducing mitochondrial oxidative stressmediated ferroptosis 2022 35249882 ADAMTS9-AS1 ENSG00000241158 lncRNA cytoplasm Homo sapiens (human) Ovarian cancer OSE CCK-8 assay ferrostatin-1 miR-587/SLC7A11 ROS ADAMTS9-AS1 attenuated ferroptosis by targeting miR-587/SLC7A11 axis Long non-coding RNA ADAMTS9-AS1 attenuates ferroptosis by Targeting microRNA-587/solute carrier family 7 member 11 axis in epithelial ovarian cancer 2022 35311457 linc00976 ENSG00000229140 lncRNA cytoplasm Homo sapiens (human) Cholangiocarcinoma HIBEC, HuCCT1, HCCC-9810, QBC939, HuH28, and RBE cell lines CCK-8 assay - miR-3202/GPX4 GPX4 linc00976 plays a crucial role in accelerating CCA tumorigenesis and metastasis and inhibiting ferroptosis by modulating the miR-3202/GPX4 axis Knockdown of linc00976 significantly repressed proliferation and metastasis and promoted ferroptosis of CCA cells both in vitro and in vivo, whereas linc00976 overexpression exerted the opposite effect. Mechanistically, linc00976 competitively interacted with miR-3202 to upregulate GPX4 expression, thus contributing to the malignant biological behavior of CCA cells. Moreover, we demonstrated that JUND specifically interacts with the linc00976 promoter and activates linc00976 transcription. Accordingly, JUND promotes linc00976 transcription, and linc00976 plays a crucial role in accelerating CCA tumorigenesis and metastasis and inhibiting ferroptosis by modulating the miR-3202/GPX4 axis. JUND/linc00976 promotes cholangiocarcinoma progression and metastasis, inhibits ferroptosis by regulating the miR-3202/GPX4 axis 2022 36400758 circ0004372 hsa_circ_0004372 circRNA cytoplasm Homo sapiens (human) Cardiovascular remodeling Human aortic advential fibroblasts CCK-8 assay ferrostatin-1 miR-124/SERTAD4 ROS UII promotes the activation of VAFs through the circ0004372/miR-124/SERTAD4/ferroptosis pathway When co-transfected with circ0004372 siRNA and miR-124 inhibitors or miR-124 mimics and SERTAD4 overexpression vector, UII still significantly increased the expression of α-SMA, Collagen I and TGF-β1. After transfection with circ0004372 overexpression vector, miR-124 inhibitors or SERTAD4 overexpression vector and then treating with UII and Ferrostatin-1, the expression of α-SMA, Collagen I and TGF-β1 was still significant; when the circ0004372 overexpression vector and miR-124 mimics or miR-124 inhibitors and SERTAD4 siRNA were co-transfected and then UII and Ferrostatin-1 were added, the expression of α-SMA, Collagen I and TGF-β1 was not significantly increased. Therefore, these results indicate that UII promotes the activation of VAFs through the circ0004372/miR-124/SERTAD4/ferroptosis pathway. Urotensin II activates the ferroptosis pathway through circ0004372/miR-124/SERTAD4 to promote the activation of vascular adventitial fibroblasts 2022 36222337 hsa-miR-744-5p MIMAT0004945 miRNA - Homo sapiens (human) Non-small cell lung cancer A549 and H1299 MTT assay - GPX4 GPX4 Propofol inhibited tumor growth and CR to Cis by upregulating miR-744-5p/miR-615-3p and inhibiting GPX4 to induce ferroptosis Propofol upregulated miR-744-5p/miR-615-3p to inhibit GPX4 transcription. Upregulation of GPX4 or downregulation of miR-744-5p/miR-615-3p attenuated the inhibitory effect of propofol on CR to Cis. In vivo, propofol inhibited tumor growth and CR to Cis by upregulating miR-744-5p/miR-615-3p and inhibiting GPX4 to induce ferroptosis. In summary, propofol inhibited GPX4-mediated ferroptosis and reduces CR of NSCLC cells to Cis through the miR-744-5p/miR-615-3p axis. Propofol decreases cisplatin resistance of non-small cell lung cancer by inducing GPX4-mediated ferroptosis through the miR-744-5p/miR-615-3p axis 2022 36427803 hsa-miR-615-3p MIMAT0003283 miRNA - Homo sapiens (human) Non-small cell lung cancer A549 and H1299 MTT assay - GPX4 GPX4 Propofol inhibited tumor growth and CR to Cis by upregulating miR-744-5p/miR-615-3p and inhibiting GPX4 to induce ferroptosis Propofol upregulated miR-744-5p/miR-615-3p to inhibit GPX4 transcription. Upregulation of GPX4 or downregulation of miR-744-5p/miR-615-3p attenuated the inhibitory effect of propofol on CR to Cis. In vivo, propofol inhibited tumor growth and CR to Cis by upregulating miR-744-5p/miR-615-3p and inhibiting GPX4 to induce ferroptosis. In summary, propofol inhibited GPX4-mediated ferroptosis and reduces CR of NSCLC cells to Cis through the miR-744-5p/miR-615-3p axis. Propofol decreases cisplatin resistance of non-small cell lung cancer by inducing GPX4-mediated ferroptosis through the miR-744-5p/miR-615-3p axis 2022 36427803 hsa-miR-338-3p MIMAT0000763 miRNA - Homo sapiens (human) Diabetic retinopathy ARPE-19 MTT assay - SLC1A5 ROS miR-338-3p/SLC1A5 axis could block high glucose-induced ferroptosis in RPE cells. miR-338-3p targeted the 3' untranslated regions (3'UTR) of SLC1A5 for its inhibition and degradation, and high glucose downregulated SLC1A5 by upregulating miR-338-3p in RPE cells. Next, the miR-338-3p inhibitor and SLC1A5 overexpression vectors were delivered into the RPE cells, and the following gain- and loss-of-function experiments validated that both miR-338-3p ablation and SLC1A5 upregulation abrogated the regulating effects of high glucose on cell proliferation, viability, ferroptosis and ROS production in RPE cells. A novel miR-338-3p/SLC1A5 axis reprograms retinal pigment epithelium to increases its resistance to high glucose-induced cell ferroptosis 2022 35320491 OGFRP1 ENSG00000182057 lncRNA - Homo sapiens (human) Lung cancer Lung cancer tissues Iron assay kit ferrostatin-1 miR-299-3p/SLC38A1 ROS OGFRP1 regulated cell proliferation and ferroptosis The interaction between miR-299-3p and OGFRP1 or solute carrier family 38 member 1 (SLC38A1) was predicted by StarbaseV3.0 and verified by dual-luciferase reporter assay and Pearson's correlation coefficient. Besides, a transplantation model of human lung cancer in nude mice was established to evaluate the role of OGFRP1 in lung cancer. OGFRP1 and SLC38A1 were overexpressed, whereas miR-299-3p was lowly expressed in lung cancer tumors and cells. OGFRP1 knockdown suppressed cell proliferation and facilitated ferroptosis by promoting lipid peroxidation and iron accumulation in lung cancer. Besides, Furthermore, miR-299-3p inhibitor or SLC38A1 overexpression attenuated OGFRP1 depletion-induced suppression on cell proliferation and ferroptosis in lung cancer. Animal experiments indicated that OGFRP1 deficiency restrained tumor growth in vivo by regulating the miR-299-3p/SLC38A1 axis. Long non-coding RNA OGFRP1 regulates cell proliferation and ferroptosis by miR-299-3p/SLC38A1 axis in lung cancer 2022 36066402 BBOX1-AS1 ENSG00000254560 lncRNA cytoplasm Homo sapiens (human) Esophageal squamous cell cancer Esophageal squamous cell cancer tissues GSH/GSSG Ratio Detection Assay Kit erastin and ferrostatin-1 miR-513a-3p/SLC7A11 ROS Downregulation of BBOX1-AS1 inhibits cell proliferation, and metastasis accelerates cell apoptosis and ferroptosis The function of BBOX1-AS1 was studied in vivo using a xenograft model and immunohistochemistry. BBOX1-AS1 expression was significantly higher in ESCC tissues, indicating poor prognosis. Inhibition of BBOX1-AS1 reduced cell proliferation, slowed cell invasion and migration, and promoted apoptosis and ferroptosis in vitro. miR-513a-3p was verified as a specific target of BBOX1-AS1 in ESCC, whereas knockdown of miR-513a-3p reversed the suppressive function of BBOX1-AS1 silencing in TE-1 cells. Moreover, solute carrier family 7 member 11 (SLC7A11) is regulated by miR-513a-3p, which is mediated by BBOX1-AS1 in ESCC cells. lncRNA BBOX1-AS1 silencing inhibits esophageal squamous cell cancer progression by promoting ferroptosis via miR-513a-3p/SLC7A11 axis 2022 36216119 CircASAP2 mmu_circ_0003832 circRNA cytoplasm mouse Diabetes nephropathy Kidney tissue ROS levels kits - miR-770-5p/SLC7A11 ROS circ ASAP2 decreased inflammation and ferroptosis in DN through SOX2/SLC7A11 by miR-770-5p Circular ASAP2 was reducing inflammation and oxidative stress in vitro model. The inhibition of ASAP2 promoted ferroptosis in model of DN. CASAP2 suppressed miR-770-5p in DN. Additionally, miR-770-5p aggravated diabetic nephropathy in mice model. MiR-770-5p promoted inflammation and oxidative stress to aggravate renal injury in mice model. MiR-770-5p was increasing inflammation and oxidative stress in vitro model. Circular ASAP2 induced SLC7A11 expression in model of DN through SOX2 by miR-770-5p. Circ ASAP2 decreased inflammation and ferroptosis in diabetic nephropathy through SOX2/SLC7A11 by miR-770-5p 2023 36153434 CERS6-AS1 ENSG00000227617 lncRNA - Homo sapiens (human) Papillary thyroid carcinoma Thyroid cancer tissues CCK-8 assay erastin miR-497-5p/LASP1 ROS Down-regulation of CERS6-AS1 reduced cell viability and amplified cell ferroptosis High level of CERS6-AS1 and LASP1 was detected in papillary thyroid cancer tissues and cells and predicted poor prognosis. In contrast, miR-497-5p was decreased in papillary thyroid cancer tissues and cells, which was positively correlated with prognosis. Silencing CERS6-AS1 suppressed cell viability and increased ferroptosis in papillary thyroid cancer. LASP1 was modulated by CERS6-AS1 through sponging miR-497-5p. Up-regulation of LASP1 or silencing miR-497-5p could weaken the effect of CERS6-AS1 on papillary thyroid cancer cells. Silencing CERS6-AS1 restrained the growth of xenografted tumors. CERS6-AS1 Facilitates Oncogenesis and Restrains Ferroptosis in Papillary Thyroid Carcinoma by Serving as a ceRNA through miR-497-5p/LASP1 Axis 2022 35777805 mmu-miR-27a MIMAT0000537 miRNA - rat Ischemia-reperfusion injury Brain MDA Assay kit - SLC7A11 Gpx4 miR-27a induces ferroptosis The target gene of miR-27a was confirmed by dual luciferase reporter gene technique. Results After cerebral ischemia reperfusion, the level of miR-27a was up-regulated and the level of SLC7A11 was down-regulated. Inhibition of miR-27a expression reduced neurological score and cerebral infarct volume, and inhibited ferroptosis after cerebral ischemia reperfusion. Conclusion In the process of cerebral ischemia and reperfusion, the up-regulated miR-27a may induce ferroptosis through inhibiting SLC7A11, thus causing brain tissue damage. miR-27a induces ferroptosis by inhibiting solute carrier family 7 member-11 (SLC7A11) and causes cerebral ischemia-reperfusion injury in rats 2022 35786456 CircRPPH1 hsa_circ_0101420 circRNA - Homo sapiens (human) Gastric cancer MKN-45, AGS, Hs-746 T, N87, HGC-27 CCK-8 assay - miR-375/SLC7A11 ROS circRPPH1 acted as an miR-375 sponge to positively regulate SLC7A11 expression, which has been confirmed to be the direct target of miR-375 in gastric cancer, and thus regulated ferroptosis Luciferase reporter and RIP assays were implemented to reveal the underlying mechanisms. MiR-375 directly bound to circRPPH1 in gastric cancer cells. And circRPPH1 acted as an miR-375 sponge to positively regulate SLC7A11 expression, which has been confirmed to be the direct target of miR-375 in gastric cancer, and thus regulated ferroptosis. Moreover, circRPPH1 promoted the stemness of gastric cancer cells dependent on the miR-375/SLC7A11. This study provides a potential target for gastric cancer progression based on the circRPPH1/miR-375/SLC7A11 regulatory axis. CircRPPH1 promotes the stemness of gastric cancer cells by targeting miR-375/SLC7A11 axis 2022 36190453 SEMA5A-IT1 - lncRNA extracellular vesicles Homo sapiens (human) Cardiomyocyte injury CCK-8 assay - miR-143-3p/SLC7A11 ROS SEMA5A-IT1 encapsulated in sEVs inhibited H/R-induced myocardial cell death via reduction of apoptosis and ferroptosis circulating sEVs packaged with SEMA5A-IT1 could be uptaken by cardiomyocyte-like cells AC16 and increased SEMA5A-IT1 expression in AC16 cells. Upregulated SEMA5A-IT1 protected cardiomyocytes against hypoxia/reoxygenation injury, confirmed by increased cell viability, reduced cell apoptosis, and inhibited ferroptosis in AC16 cells. Mechanistically, SEMA5A-IT1 regulated the expression of B-cell CLL/lymphoma 2 (BCL2) and solute carrier family 7 member 11 (SLC7A11) through sponging miR-143-3p. Transfection of miR-143-3p mimics, BCL2, or SLC7A11 knockdown could attenuate the protective effect of SEMA5A-IT1 on cardiomyocytes. Circulating small extracellular vesicle-encapsulated SEMA5A-IT1 attenuates myocardial ischemia–reperfusion injury after cardiac surgery with cardiopulmonary bypass 2022 36284269 circ-Carm1 mmu_circ_0001751 circRNA cytoplasm mouse Acute cerebral infarction injuries HT22 CCK-8 assay erastin miR-3098-3p/ACSL4 GPX4 circ-Carm1 is upregulated in ACI. circ-Carm1 suppression protects HT22 cells from dysfunction by inhibiting ferroptosis The binding relationships between mRNAs and miRNAs were verified. circ-Carm1 was highly expressed in OGD/R-treated HT22 cells. Deficiency of circ-Carm1 restored cell viability and suppressed ferroptosis in OGD/R-induced HT22 cells. miR-3098-3p was predicted to be a target of circ-Carm1. The miR-3098-3p inhibitor partly neutralized the functions of circ-Carm1 in OGD/R-induced HT22 cells. Furthermore, acyl-CoA synthetase long-chain family member 4 (ACSL4) was confirmed to be a downstream target of miR-3098-3p and was elevated in OGD/R-induced HT22 cells. Overexpression of ACSL4 mitigated the functions of miR-3098-3p and accelerated HT22 cell dysfunction. Depletion of mmu_circ_0001751 (circular RNA Carm1) protects against acute cerebral infarction injuries by binding with microRNA-3098-3p to regulate acyl-CoA synthetase long-chain family member 4 2022 35114894 rno-miR-27a-3p MIMAT0000799 miRNA - rat Cerebral ischemia-reperfusion MDA detection kit ferrostatin-1 SLC7A11 GPX4 miR-27a may induce ferroptosis The relative expression levels of glutathione peroxidase 4(GPx4), solute carrier family 7 member 11 (SLC7A11) proteins were analyzed by Western Blot. The contents of GSH, Fe and malonaldehyde (MDA) were detected by corresponding detection kits, and the target gene of miR-27a was confirmed by dual luciferase reporter gene technique. It was found the relative expression level of miR-27a was increased and ferroptosis was aggravated as reperfusion time went by. Also, brain tissue injury and ferroptosis were exacerbated with agomiR-27a intervention, while these effects were reversed with antagomiR-27a intervention. In addition, the combined intervention of agomiR-27a and Fer-1 alleviated the brain tissue injury and ferroptosis. MicroRNA-27a Regulates Ferroptosis Through SLC7A11 to Aggravate Cerebral ischemia-reperfusion Injury 2022 36456793 circP4HB hsa_circ_0046263 circRNA cytoplasm Homo sapiens (human) Lung adenocarcinoma H1299, A549, SPCA1 and H358 CCK-8 assay erastin miR-1184/SLC7A11 ROS circP4HB acts as a novel ferroptosis suppressor in LUAD CircP4HB expression levels were increased in LUAD. It triggered glutathione (GSH) synthesis and, therefore protected LUAD cells from ferroptosis induced by erastin. CircP4HB may function as a competing endogenous RNA by modulating miR-1184 to regulate SLC7A11. CircP4HB inhibited ferroptosis by regulating miR-1184/ SLC7A11-mediated GSH synthesis. In vivo, overexpression of circP4HB promoted tumor growth and inhibited ferroptosis. CircP4HB regulates ferroptosis via SLC7A11-mediated glutathione synthesis in lung adenocarcinoma 2022 35399564 PCAT1 ENSG00000253438 lncRNA - Homo sapiens (human) Prostate cancer PC3 and 22RV1 CCK-8 assay erastin c-Myc/miR-25-3p/SLC7A11 ROS Overexpression of PCAT1 inhibited ferroptosis Overexpression of PCAT1 inhibited ferroptosis and increased docetaxel resistance, which could be attenuated by PCAT1 knockdown. Furthermore, we revealed that PCAT1 inhibited ferroptosis by activating solute carrier family 7-member 11 (SLC7A11) expression via reducing iron accumulation and subsequent oxidative damage. Mechanistically, we demonstrated that PCAT1 interacted with c-Myc and increased its protein stability using nucleotides 1093-1367 of PCAT1 and 151-202 amino acids of c-Myc protein, thereby transcriptionally promoting SLC7A11 expression. In addition, PCAT1 facilitated SLC7A11 expression by competing for microRNA-25-3p. Finally, transcription factor AP-2 gamma (TFAP2C) activated PCAT1 expression at the transcriptional level to reduce ferroptosis susceptibility and enhance chemoresistance. TFAP2C-Mediated lncRNA PCAT1 Inhibits Ferroptosis in Docetaxel-Resistant Prostate Cancer Through c-Myc/miR-25-3p/SLC7A11 Signaling 2022 35402284 circLMO1 hsa_circ_0021087 circRNA cytoplasm Homo sapiens (human) Cervical cancer Cervical cancer tissues CCK-8 assay erastin miR-4291/ACSL4 ROS CircLMO1 promoted cervical cancer cell ferroptosis The level of circLMO1 was down-regulated in cervical cancer tissues and was associated with the International Federation of Gynecology and Obstetrics (FIGO) staging. Functionally, circLMO1 overexpression inhibited cervical cancer growth and metastasis both in vitro and in vivo, whereas circLMO1 depletion promoted cervical cancer cell proliferation and invasion. Mechanistically, circLMO1 acted as a competing endogenous RNA (ceRNA) by sponging miR-4192 to repress target gene ACSL4. CircLMO1 promoted cervical cancer cell ferroptosis through up-regulating ACSL4 expression. Overexpression of miR-4291 or knockdown of ACSL4 reversed the effect of circLMO1 on facilitating ferroptosis and repressing cervical cancer cell proliferation and invasion. Circular RNA circLMO1 Suppresses Cervical Cancer Growth and Metastasis by Triggering miR-4291/ ACSL4-Mediated Ferroptosis 2022 35321435 mmu-miR-375-3p MIMAT0000739 miRNA - mice Ulcerative colitis Colonic tissue CCK-8 assay - SLC11A2 GPX4 Knockdown of miR-375-3p neutralized the role of silencing IRF7 in alleviating ferroptosis of colonic ECs Chromatin immunoprecipitation and dual-luciferase assays showed that binding of IRF7 to the miR-375-3p promoter inhibited miR-375-3p expression, and miR-375-3p suppressed SLC11A2 transcription. The rescue experiments revealed that knockdown of miR-375-3p neutralized the role of silencing IRF7 in alleviating ferroptosis of colonic ECs. Overall, IRF7 upregulated SLC11A2 transcription by inhibiting miR-375-3p expression, thereby prompting ferroptosis of colonic ECs and UC progression in DSS-treated mice. Promotive role of IRF7 in ferroptosis of colonic epithelial cells in ulcerative colitis by the miR-375-3p/SLC11A2 axis 2022 36336986 circ_0000190 hsa_circ_0000190 circRNA - Homo sapiens (human) Gastric cancer AGS, KATOⅢ, MKN1 and HGC27 CCK-8 assay erastin miR-382-5p/ZNRF3 ROS Circ_0000190 suppresses cell proliferation and induces the ferroptosis of GC cells Low expression of circ_0000190 predicted dismal prognosis in GC patients. Circ_0000190 overexpression inhibited the proliferation, migration and invasion and promoted Erastin- or ras selective lethal 3 (RSL3)-mediated ferroptosis in GC cells. MiR-382-5p was a target of circ_0000190, and circ_0000190 suppressed GC progression partly via serving as miR-382-5p sponge. ZNRF3 was a target of miR-382-5p, and miR-382-5p accelerated the proliferation, motility and restrained the ferroptosis of GC cells partly via regulating ZNRF3. Circ_0000190 sponges miR-382-5p to suppress cell proliferation and motility and promote cell death by targeting ZNRF3 in gastric cancer 2022 35037032 circPVT1 hsa_circ_0085536 circRNA - Homo sapiens (human) Esophageal carcinoma EC9706 and KYSE70 CCK-8 assay - miR-30a-5p/FZD3 GPX4 knockdown of circPVT1 increased ferroptosis CircPVT1 was significantly upregulated in ESCC cells resistant to 5-FU. Knockdown of circPVT1 enhanced the 5-FU chemosensitivity of ESCC cells resistant to 5-FU by increasing cytotoxicity and downregulating multidrug-resistant associated proteins, including P-gp and MRP1. Luciferase assay showed that circPVT1 acted as a sponge of miR-30a-5p, and Frizzled3 (FZD3) was a downstream target of miR-30a-5p. The enhanced 5-FU chemosensitivity by circPVT1 knockdown was reversed with miR-30a-5p inhibitor. Besides, the increased 5-FU chemosensitivity by miR-30a-5p mimics was reversed with FZD3 overexpression. Furthermore, knockdown of circPVT1 increased ferroptosis through downregulating p-β-catenin, GPX4, and SLC7A11 while miR-30a-5p inhibition and FZD3 overexpression reversed the phenotype by upregulating p-β-catenin, GPX4, and SLC7A11. Circular RNA CircPVT1 Inhibits 5-Fluorouracil Chemosensitivity by Regulating Ferroptosis Through MiR-30a-5p/FZD3 Axis in Esophageal Cancer Cells 2021 34966683 circ-BGN hsa_circ_0091740 circRNA cytoplasm Homo sapiens (human) Breast cancer BT474 and SKBR3 GSH/GSSG Ratio Detection Assay erastin OTUB1 and SLC7A11 ROS circ-BGN was able to physically interact with OTUB1 and SLC7A11, resulting in increasing SLC7A11 protein stability, thereby inhibiting ferroptosis Further, we found that circ-BGN could directly bind to OTUB1 and SLC7A11, enhancing OTUB1-mediated SLC7A11 deubiquitination and thereby inhibiting ferroptosis, a newly recognized form of cell death that is distinct from apoptosis, necrosis, and autophagy. Moreover, erastin, a small-molecule ferroptosis inducer, could effectively restore the anti-tumor effect of trastuzumab. A novel circular RNA confers trastuzumab resistance in human epidermal growth factor receptor 2-positive breast cancer through regulating ferroptosis 2022 35234341 circACAP2 hsa_circ_0068565 circRNA - Homo sapiens (human) Cervical cancer SiHa and HeLa Iron assay kit - miR-193a-5p/GPX4 GPX4 circACAP2 repressed ferroptosis of cervical cancer The circACAP2 served as a ceRNA of miR-193a-5p and directly interacted with miR-193a-5p in cervical cancer cells. miR-193a-5p was able to target GPX4 and circACAP2 promoted GPX4 expression by sponging miR-193a-5p in cervical cancer cells. The knockdown of circACAP2 inhibited the cervical cancer cell viability, but the miR-193a-5p inhibitor or GPX4 overexpression could reverse the effect in the cells. The inhibition of miR-193a-5p or GPX4 overexpression repressed the circACAP2 depletion-induced levels of lipid ROS, iron, and Fe2+ in cervical cancer cells. Circular RNA circACAP2 Suppresses Ferroptosis of Cervical Cancer during Malignant Progression by miR-193a-5p/GPX4 2022 35847361 CircLRFN5 hsa_circ_0031751 circRNA cytoplasm Homo sapiens (human) Glioblastoma Glioma tissues BODIPY 581/591 C11 kit ferrostatin-1, RSL PRRX2/GCH1 ROS circLRFN5 downregulates PRRX2 mediated transcription of GCH1 in GSCs. GCH1 is responsible for suppressing ferroptosis We found a novel circRNA circLRFN5 is downregulated in GBM and associated with GBM patients’ poor prognosis. CircLRFN5 overexpression inhibits the cell viabilities, proliferation, neurospheres formation, stemness and tumorigenesis of GSCs via inducing ferroptosis. Mechanistically, circLRFN5 binds to PRRX2 protein and promotes its degradation via a ubiquitin-mediated proteasomal pathway. PRRX2 can transcriptionally upregulate GCH1 expression in GSCs, which is a ferroptosis suppressor via generating the antioxidant tetrahydrobiopterin (BH4). CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis 2022 36266731 CircEXOC5 hsa_circ_0102187 circRNA - mouse Sepsis causes severe acute lung injury Mouse lung microvascular endothelial cells T-GSH/GSSG determination kit - PTBP1/ACSL4 ROS circEXOC5 aggravated ferroptosis Our results showed that the circEXOC5 expression was significantly increased in the in vivo and in vitro models of sepsis. And after inhibiting circEXOC5, it improved the lung injury of septic mice. It was confirmed in cell models that ROS levels and ferroptosis in cells were reduced after knocking down circEXOC5. In addition, the expressions of ACSL4 and Gpx4 proteins were regulated by the level of circEXOC5. Finally, we also found that circEXOC5 had a direct binding relationship with PTBP1. CircEXOC5 promotes ferroptosis by enhancing ACSL4 mRNA stability via binding to PTBP1 in sepsis-induced acute lung injury 2022 35709678 circST6GALNAC6 hsa_circ_0088708 circRNA cytoplasm Homo sapiens (human) Bladder cancer UM-UC-3 and J82 Prussian Blue Iron Stain Kit erastin HSPB1/P38 ROS CircST6GALNAC6 inhibits HSPB1 and promotes cell ferroptosis Mechanistic studies revealed that circST6GALNAC6 bound to the N-terminus of small heat shock protein 1 (HSPB1) and thus blocked the erastin-induced phosphorylation of HSPB1 at the Ser-15 site, a phosphorylation site in the protective response to ferroptosis stress. In addition, protein kinase C inhibited circST6GALNAC6-induced ferroptosis by increasing the overall phosphorylation level of HSPB1, further demonstrating the role of phosphorylation activation of HSPB1 in resistance to ferroptosis. Finally, the involvement of the HSPB1/p38 MAPK pathway in the downstream signal transduction of circST6GALNAC6 in bladder cancer ferroptosis regulation was determined. The regulatory mechanism of ferroptosis sensitivity dependent on circST6GALNAC6 expression levels in bladder cancer was revealed as circRNA regulation of various protein functions. CircRNA-ST6GALNAC6 increases the sensitivity of bladder cancer cells to erastin-induced ferroptosis by regulating the HSPB1/P38 axis 2022 35945269 CircRAPGEF5 hsa_circ_0001681 circRNA cytoplasm Homo sapiens (human) Endometrial cancer Endometrial cancer tissues Iron assay Kit erastin and RSL3 RBFOX2 ROS circRAPGEF5 promote the formation of TFRC with exon-4 skipping and confer ferroptosis resistance in EC cells Elevated levels of circRAPGEF5 lead to ferroptosis resistance via the decreased labile iron pool and attenuated lipid peroxide production in EC cells. Additionally, a series of gain- and loss-of-function experiments demonstrated that knocking down or overexpressing RBFOX2 reversed the effects of knocking down or overexpressing circRAPGEF5 in EC cells. Finally, it is revealed that circRAPGEF5 promote the formation of TFRC with exon-4 skipping and confer ferroptosis resistance in EC cells through the interaction with RBFOX2. Collectively, these findings provide new insight into the molecular mechanism in which circRNAs mediate mediates ferroptosis via modulating alternative splicing, and circRAPGEF5/RBFOX2 splicing axis could be a promising therapeutic target for treating EC. CircRAPGEF5 interacts with RBFOX2 to confer ferroptosis resistance by modulating alternative splicing of TFRC in endometrial cancer 2022 36182807 circSnx12 hsa_circ_0090971 circRNA cytoplasm Homo sapiens (human) Ovarian cancer SKOV3 and A2780 CCK-8 assay erastin miR-194-5p/SLC7A11 lipid peroxidation circSnx12 ameliorates cisplatin resistance by blocking ferroptosis We studied the ferroptosis-associated circRNA circSnx12. We evaluated circSnx12 expression in OC cell lines and tissues that were susceptible or resistant to cisplatin using quantitative real-time PCR. We also conducted in vitro and in vivo assays examining the function and mechanism of lnc-LBCSs. Knockdown of circSnx12 rendered cisplatin-resistant OC cells more sensitive to cisplatin in vitro and in vivo by activating ferroptosis, which was at least partially abolished by downregulation of miR-194-5p. Molecular mechanics studies indicate that circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in OC. circRNA circSnx12 confers Cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis 2023 36617466 CircSCN8A hsa_circ_0026337 circRNA cytoplasm Homo sapiens (human) Non-small cell lung cancer Non-small cell lung cancer tissues Iron Assay Kit erastin and ferrostatin-1 miR-1290/ACSL4 GPX4 circSCN8A represses cell proliferation and metastasis in NSCLC by regulating the miR-1290/ACSL4 axis to induce ferroptosis CircSCN8A suppressed cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro and blocked tumor growth in vivo. Moreover, circSCN8A promoted cell ferroptosis in NSCLC. Mechanistically, circSCN8A acted as a competing endogenous RNA (ceRNA) by sponging miR-1290 to enhance the expression of long-chain acyl-CoA synthetase-4 (ACSL4). Furthermore, the knockdown of ACSL4 or overexpression of miR-1290 reversed the effect of circSCN8A on facilitating ferroptosis and inhibiting cell proliferation and metastasis. In summary, circSCN8A represses cell proliferation and metastasis in NSCLC by regulating the miR-1290/ACSL4 axis to induce ferroptosis. CircSCN8A suppresses malignant progression and induces ferroptosis in non-small cell lung cancer by regulating miR-1290/ACSL4 axis 2022 36482742 CBSLR tcons0001221 lncRNA cytoplasm Homo sapiens (human) Gastric cancer MKN45 and MKN28 CellTiter-Glo luminescent cell viability assay ferrostatin-1 YTHDF2/CBS GPX4 CBSLR inhibits ferroptosis by modulating ACSL4 methylation CBSLR interacted with YTHDF2 to form a CBSLR/YTHDF2/CBS signaling axis that decreased the stability of CBS mRNA by enhancing the binding of YTHDF2 with the m6A-modified coding sequence (CDS) of CBS mRNA. Furthermore, under decreased CBS levels, the methylation of the ACSL4 protein was reduced, leading to protein polyubiquitination and degradation of ACSL4. This, in turn, decreased the pro-ferroptosis phosphatidylethanolamine (PE) (18:0/20:4) and PE (18:0/22:4) content and contributed to ferroptosis resistance. Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer 2021 35499052 HEPFAL LINC03038 lncRNA cytoplasm Homo sapiens (human) Hepatocellular carcinoma HEK293T cells and PLC/PRF/5 cells GSH-Glo Glutathione Assay Kit erastin SLC7A11 ROS HEPFAL can promote ferroptosis by reducing the expression of SLC7A11 This study shows that the expression of the long noncoding RNA HEPFAL was reduced in HCC tissues. We found that lncRNA HEPFAL can promote ferroptosis by reducing the expression of solute carrier family 7 member 11 (SLC7A11) and increasing the levels of lipid reactive oxygen species (ROS) and iron (two surrogate markers of ferroptosis). In addition, we found that lncRNA HEPFAL increases the sensitivity of erastin-induced ferroptosis, which may be related to mTORC1, and lncRNA HEPFAL can promote the ubiquitination of SLC7A11 and reduce the stability of the SLC7A11 protein, resulting in decreased expression. Understanding these mechanisms indicates that lncRNAs related to ferroptosis are essential for the occurrence and treatment of HCC. LncRNA HEPFAL accelerates ferroptosis in hepatocellular carcinoma by regulating SLC7A11 ubiquitination 2022 36008384 BDNF-AS ENSG00000245573 lncRNA nucleus Homo sapiens (human) Gastric cancer AGS, HGC-27, BGC-823, MGC-803 and MKN-45 lipid ROS kit erastin and RSL3 WDR5/FBXW7 ROS BDNF-AS facilitated GC formation and PM by regulating ferroptosis BDNF-AS overexpression protected GC cells from ferroptosis and promoted the progression of GC and PM. Mechanistically, BDNF-AS could regulate FBXW7 expression by recruiting WDR5, thus affecting FBXW7 transcription, and FBXW7 regulated the protein expression of VDAC3 through ubiquitination. Conclusively, our research demonstrated that the BDNF-AS/WDR5/FBXW7 axis regulates ferroptosis in GC by affecting VDAC3 ubiquitination. BDNF-AS might be a biomarker for the evaluation of GC prognosis and the treatment of GC. The lncRNA BDNF-AS/WDR5/FBXW7 axis mediates ferroptosis in gastric cancer peritoneal metastasis by regulating VDAC3 ubiquitination 2022 35280682 TUG1 ENSG00000253352 lncRNA exosome Homo sapiens (human) Ischemic/reperfusion injury HK2 cells Iron Assay Kit/ROS Assay Kit ferrostatin-1 ASCL4 ROS LncRNA TUG1 suppresses H/R-induced ferroptosis USC-Exo treatment improved kidney injury and ameliorated ferroptosis in IRI-induced AKI mouse models. USC-Exo were rich in lncRNA TUG1, which suppressed ferroptosis in HK-2 cells exposed to H/R. Mechanistically, lncRNA TUG1 regulates the stability of ACSL4 mRNA by interacting with RNA-binding protein SRSF1. In addition, SRSF1 upregulation or ACSL4 downregulation partially reversed the protective effect of lncRNA TUG1 on ferroptosis in H/R-treated HK-2 cells. Further, ACSL4 upregulation partially reversed TUG1's repression on kidney injury and ferroptosis in IRI-induced AKI mice. Exosomal lncRNA TUG1 derived from human urine-derived stem cells attenuates renal ischemia/reperfusion injury by interacting with SRSF1 to regulate ASCL4-mediated ferroptosis 2022 35841017 MALAT1 ENSG00000251562 lncRNA cytoplasm Homo sapiens (human) Endometriosis endometriosis tissues CCK-8 assay erastin miR-145-5p/MUC1 MUC1 Silencing of lncRNA MALAT1 facilitates erastin-induced ferroptosis We demonstrated that MALAT1 served as a competing endogenous RNA of miR-145-5p to regulate the expression of MUC1, a suppressor of ferroptosis. MALAT1 knockdown-mediated ferroptotic cell death and MUC1 downregulation could be abrogated by inhibition of miR-145-5p. In addition, miR-145-5p inhibition-mediated ferroptotic cell death could be abolished by MUC1 knockdown. Furthermore, erastin-induced ferroptosis shrunk endometriotic lesions via the MALAT1/miR-145-5p/MUC1 axis in vivo. Taken together, our data indicate that knockdown of MALAT1 facilitates ferroptosis upon erastin treatment via miR-145-5p/MUC1 signaling. Silencing of lncRNA MALAT1 facilitates erastin-induced ferroptosis in endometriosis through miR-145-5p/MUC1 signaling 2022 35399101 Mir9-3hg ENSMUSG00000097023 lncRNA exosome mouse Cardiovascular disease BMSCs CCK-8 assay - Pum2/PRDX6 Gpx4 and GSH BMSCs-Exo Mir9-3hg attenuates H/R-induced ferroptosis BMSCs-Exo treatment attenuates I/R-induced cardiac injury by inhibiting cardiomyocyte ferroptosis through modulating the Pum2/PRDX6 axis, thereby ameliorating cardiac function. The BMSC-derived exosomal lncRNA Mir9-3hg suppresses cardiomyocyte ferroptosis in ischemia-reperfusion mice via the Pum2/PRDX6 axis 2021 34953631 AAB AABR07017145.1 lncRNA - Homo sapiens (human) Cardiac hypertrophy Neutrophils Iron Assay Kit, fluorescence microscopy ferrostatin-1 ( miR-30b-5p/TIMP1 ROS lncRNA AAB was remarkably upregulated in cardiac hypertrophy rats and this upregulation promoted ferroptosis We found that lncRNA AAB sponged and sequestered miR-30b-5p to induce the imbalance of MMP9/TIMP1, which enhanced the activation of transferrin receptor 1 (TFR-1) and then eventually led to the ferroptosis of CMECs. Moreover, we have developed a delivery system based on neutrophil membrane (NM)-camouflaged mesoporous silica nanocomplex (MSN) for inhibition of cardiac hypertrophy, indicating the potential role of silenced lncRNA AAB (si-AAB) and overexpressed miR-30b-5p as the novel therapy for cardiac hypertrophy. Neutrophil-like cell membrane-coated siRNA of lncRNA AABR07017145.1 therapy for cardiac hypertrophy via inhibiting ferroptosis of CMECs 2022 34938604 A2M-AS1 ENSG00000245105 lncRNA nucleus and cytoplasm Homo sapiens (human) Pancreatic cancer PANC-1, AsPC-1 and HPDE Iron assay kit, GSH detection kit erastin PCBP3 p38 and AKT/mTOR The overexpression of A2M-AS1 promoted ferroptosis The Erastin-induced ferroptosis increased the expression levels of A2M-AS1. The overexpression of A2M-AS1 promoted ferroptosis in the pancreatic cancer, which was inhibited by the silencing of A2M-AS1. Mechanically, A2M-AS1 could directly interact with the poly (rC) binding protein 3 (PCBP3), which plays an important role in the process of iron metabolism, thereby promoting the ferroptosis in pancreatic cancer. In addition, the A2M-AS1/PCBP3 axis could facilitate the p38 activation and inhibit the phosphorylation of the AKT-mTOR signaling pathway; all these participate in regulating ferroptosis. LncRNA A2M-AS1 Promotes Ferroptosis in Pancreatic Cancer via Interacting With PCBP3 2022 35920801 LncAABR07025387.1 lncAABR07025387.1 lncRNA cytoplasm rat Myocardial ischemia/reperfusion H9C2 and HEK293T Fluorescence microscope - miR-205/ACSL4 ROS LncAABR07025387.1 Inhibition Enhances Cell Viability and Suppresses ACSL4-Mediated Ferroptosis Silencing lncAABR07025387.1 improved MI/R injury in vivo and inhibited myocardial cell ferroptosis under H/R conditions. Bioinformatics analyses and luciferase, pull-down, and RNA-binding immunoprecipitation assays further revealed that lncAABR07025387.1 interacted with miR-205, which directly targeted ACSL4, a known contributor to ferroptosis. Furthermore, downregulating miR-205 reversed the ACSL4 inhibition induced by silencing lncAABR07025387.1. These findings suggest that, mechanistically, lncAABR07025387.1 negatively regulates miR-205 expression and subsequently upregulates ACSL4-mediated ferroptosis. LncAABR07025387.1 Enhances Myocardial Ischemia/Reperfusion Injury Via miR-205/ACSL4-Mediated Ferroptosis 2022 35186915 OIP5-AS1 ENSG00000247556 lncRNA - Homo sapiens (human) Oesophageal carcinoma Eca109, TE-13, TE-1, and TTN CCK-8 Assay erastin and RSL3 GPX4 GPX4 OIP5-AS1 Induced Apoptosis OIP5-AS1 inhibition significantly inhibited EC cell viability and proliferation, induced ferroptosis, and downregulated GPX4 levels, while GPX4 reversed these effects. OIP5-AS1/GPX4 induced CD8+ T cell interaction and induced apoptosis through PD-1/PD-L1 immune checkpoints of CD8+ T cells. LncRNA OIP5-AS1 Knockdown Facilitated the Ferroptosis and Immune Evasion by Modulating the GPX4 in Oesophageal Carcinoma 2022 35872956 Uc.339 - lncRNA - Homo sapiens (human) Lung cancer A549, H1299, 16HBE and PC-9 GSH detection kit, ROS assay kit - miR-339/SLC7A11 ROS Uc.339/miR-339/SLC7A11 axis mediated lung cancer metastasis by influencing ferroptosis The Uc.339/miR-339/SLC7A11 axis regulated the proliferation, migration and invasion of A549 and H1299cells in vitro by affecting ferroptosis. Finally, in mouse xenograft models, knocking down Uc.339 in LLC cells was able to inhibits tumor growth by blocking the axis of Uc.339/miR-339/SLC7A11 in vivo, but miR-339 inhibitors could reverse this inhibition. Taken together, our results uncovered a Uc.339/miR-339/SLC7A11 axis that leads to defects in the ferroptosis in lung cancer, and constitutes a potential mechanism that drives the metastasis of lung adenocarcinoma. LncRNA T-UCR Uc.339/miR-339/SLC7A11 Axis Regulates the Metastasis of Ferroptosis-Induced Lung Adenocarcinoma 2022 35399708 AGAP2-AS1 ENSG00000255737 lncRNA - Homo sapiens (human) Melanoma Melanoma cells CCK-8 assay erastin SLC7A11 IGF2BP2 Pathway AGAP2-AS1 Prevents Ferroptosis lncRNA AGAP2-AS1 Facilitates Tumorigenesis and Ferroptosis Resistance through SLC7A11 by IGF2BP2 Pathway in Melanoma 2022 35707044 LINC00597 LINC00597 lncRNA - Homo sapiens (human) Lung cancer A549, SK-MES-1 and 293T Iron Colorimetric Assay Kit - hsa-miR-367-3p/TFRC TFRC cinobufotalin induced ferroptosis in lung cancer cells through lncRNA LINC00597/hsa-miR-367-3p/TFRC pathway via resibufogenin. This study indicated that cinobufotalin suppressed lung cancer cell growth through resibufogenin. Besides, cinobufotalin induced ferroptosis in lung cancer cells through resibufogenin. Moreover, cinobufotalin increased lncRNA LINC00597 level whereas downregulated hsa-miR-367-3p expression in lung cancer cells via resibufogenin. In addition, ferroptosis inducer transferrin receptor (TFRC) was the target of hsa-miR-367-3p, and lncRNA LINC00597 upregulates TFRC expression through sponging hsa-miR-367-3p in lung cancer cells. Cinobufotalin induces ferroptosis to suppress lung cancer cell growth by lncRNA LINC00597\hsa-miR-367-3p\TFRC pathway via resibufogenin 2022 36221890 LINC00239 LINC00239 lncRNA cytoplasm Homo sapiens (human) Colorectal cancer RKO, HCT116, CaCo2, SW480, SW620 - erastin and RSL3 Nrf2 Keap1/Nrf2 signaling pathway LINC00239 regulates ferroptosis by modulating the expression of Keap1/Nrf2 signaling pathway Long noncoding RNA LINC00239 inhibits ferroptosis in colorectal cancer by binding to Keap1 to stabilize Nrf2 2022 36038548 NEAT1 ENSG00000245532 lncRNA exosomes rat sepsis-associated encephalopathy bEnd.3 CCK-8 assay FeCl3 miR-9-5p/TFRC/GOT1 GSH, GPX4 and ROS Overexpression of NEAT1 enhanced ferroptosis stress In conclusion, these findings suggest that sepsis induced high expression of serous exosome-derived NEAT1, and it might exacerbate SAE by promoting ferroptosis through regulating miR-9-5p/TFRC and GOT1 axis. Exosome-Derived lncRNA NEAT1 Exacerbates Sepsis-Associated Encephalopathy by Promoting Ferroptosis Through Regulating miR-9-5p/TFRC and GOT1 Axis 2022 35727437 PMAN - lncRNA - Homo sapiens (human) gastric cancer AGS and MGC-803 CCK-8 assay Erastin SLC7A11 ROS and GSH PMAN-OE promoted resistance to ferroptosis These results indicated that PMAN-OE promoted resistance to ferroptosis in MGC-803 cells. Taken together, these results demonstrated that PMAN-SH increased the sensitivity of AGS cells to ferroptosis. Hypoxia-induced HIF-1α/lncRNA-PMAN inhibits ferroptosis by promoting the cytoplasmic translocation of ELAVL1 in peritoneal dissemination from gastric cancer 2022 35864064 lncFAL - lncRNA - Homo sapiens (human) hepatocellular carcinoma PLC5 and Huh7 CCK-8 assay erastin and ferrostatin-1 FSP1 ROS HCC cells overexpressing lncFAL exhibited decreased vulnerability to ferroptosis Although HDLBP or lncFAL could not regulate the GPX4 antioxidant signalling pathway, lncFAL reduced ferroptosis vulnerability by directly binding to ferroptosis suppressor protein 1 (FSP1) and competitively abolishing Trim69-dependent FSP1 polyubiquitination degradation. HDLBP-stabilized lncFAL inhibits ferroptosis vulnerability by diminishing Trim69-dependent FSP1 degradation in hepatocellular carcinoma 2022 36423520 TUG1 ENSG00000253352 lncRNA - Homo sapiens (human) glioma U87 and U251 CCK-8 assay Ferrostatin-1 MAZ ROS overexpressed TUG1 could enhance ferroptosis TUG1 Targets MAZ and Regulates Ferroptosis Induced by DHA TUG1/MAZ/FTH1 Axis Attenuates the Antiglioma Effect of Dihydroartemisinin by Inhibiting Ferroptosis 2022 36164395 SNHG14 ENSG00000224078 lncRNA - Homo sapiens (human) osteosarcoma NR-SJSA1 MTT assay ferrostatin-1 miR-206 /SLC7A11 ROS LncRNA SNHG14 knockdown promotes ferroptosis in NR-SJSA1 cells Mechanistically, lncRNA SNHG14 targeted and down-regulated the expression of miR-206, further affecting the common ferroptosis inhibitor SLC7A11, and preventing NR-SJSA1 cells from undergoing ferroptosis. LncSNHG14 promotes nutlin3a resistance by inhibiting ferroptosis via the miR-206 /SLC7A11 axis in osteosarcoma cells 2023 36599973 ATXN8OS ENSG00000230223 lncRNA cytoplasm Homo sapiens (human) glioma U251TR CCK-8 assay - ADAR/GLS2 ROS ATXN8OS could facilitate ferroptosis In conclusion, ATXN8OS mediated ferroptosis and regulated the TMZ-resistance of glioma via ADAR/GLS2 pathway. Long non-coding RNA ATXN8OS promotes ferroptosis and inhibits the temozolomide-resistance of gliomas through the ADAR/GLS2 pathway 2022 35460867 LINC01134 ENSG00000236423 lncRNA - Homo sapiens (human) Hepatocarcinoma HepG2 and Huh-7 CCK-8 assay erastin Nrf2/GPX4 GSH, GPX4 and ROS Silenced LINC01134 Enhances the Sensitivity of Ferroptosis Inducers Silenced LINC01134 Enhances the Sensitivity of Ferroptosis Inducers Silenced LINC01134 Enhances Oxaliplatin Sensitivity by Facilitating Ferroptosis Through GPX4 in Hepatocarcinoma 2022 35875091 H19 ENSG00000130600 lncRNA - Homo sapiens (human) Spontaneous abortion placental villi tissue and HTR-8/SVneo cells CCK-8 assay ferrostatin-1 GPX4 GPX4 H19 has important roles in SA by promoting apoptosis and ferroptosis It was demonstrated that silencing H19 downregulated Bcl-2 and GPX4 expression and upregulated Bax expression at both the mRNA and protein levels in HTR-8/SVneo trophoblast cells. In conclusion, the present findings suggested that H19 has important roles in SA by promoting apoptosis and ferroptosis. Long non-coding RNA H19 regulates Bcl-2, Bax and phospholipid hydroperoxide glutathione peroxidase expression in spontaneous abortion 2021 33273971 cir93 circRNA_101093 circRNA exosome Homo sapiens (human) Lung adenocarcinoma H1650, PC9, H1975, H358, A549, and H1299 cell lines CCK-8 assay erastin and RSL3 FABP3 ROS cir93 are essential for desensitizing LUAD cells to ferroptosis Plasma exosome from LUAD patients specifically reduced lipid peroxidation and desensitized LUAD cells to ferroptosis. A potential explanation is that exosomal circRNA_101093 (cir93) maintained an elevation in intracellular cir93 in LUAD to modulate AA, a poly-unsaturated fatty acid critical for ferroptosis-associated increased peroxidation in the plasma membrane. Mechanistically, cir93 interacted with and increased fatty acid-binding protein 3 (FABP3), which transported AA and facilitated its reaction with taurine. Thus, global AA was reduced, whereas N-arachidonoyl taurine (NAT, the product of AA and taurine) was induced. Notably, the role of NAT in suppressing AA incorporation into the plasma membrane was also revealed. Essential roles of exosome and circRNA_101093 on ferroptosis desensitization in lung adenocarcinoma 2022 35184419