RBM15 promotes hypoxia/reoxygenation-induced ferroptosis in human cardiomyocytes by mediating m6A modification of ACSL4
Abstract Background Acute myocardial infarction (AMI) refers to the acute necrosis of part of the myocardium caused by persistent and severe myocardial ischemia. The aim of the study was to investigate the effect of RNA binding motif protein 15 (RBM15) and acyl-CoA synthetase long chain family membe...
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BMC
2025-07-01
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| Series: | Hereditas |
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| Online Access: | https://doi.org/10.1186/s41065-025-00453-0 |
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| author | Yi Cheng Jiamin Wan Yingyue Xu Shasha Liu Linfeng Li Jing Zhou Fuyan Xie |
| author_facet | Yi Cheng Jiamin Wan Yingyue Xu Shasha Liu Linfeng Li Jing Zhou Fuyan Xie |
| author_sort | Yi Cheng |
| collection | DOAJ |
| description | Abstract Background Acute myocardial infarction (AMI) refers to the acute necrosis of part of the myocardium caused by persistent and severe myocardial ischemia. The aim of the study was to investigate the effect of RNA binding motif protein 15 (RBM15) and acyl-CoA synthetase long chain family member 4 (ACSL4) on ischemia/reperfusion (I/R)-induced ferroptosis of cardiomyocytes. Methods and results AC16 cells were treated with hypoxia/reoxygenation (H/R) to establish an in vitro myocardial infarction cell model. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay were used to determine gene expression. Cell Counting Kit-8 (CCK-8) assay was conducted to investigate cell viability. Ferroptosis level was evaluated by commercial kits. N6-methyladenosine (m6A) level was examined by M6A quantification analysis. RNA immunoprecipitation (RIP) assay, methylated RNA Immunoprecipitation (meRIP) assay and dual-luciferase reporter assay were adopted to verify the combination between RBM15 and ACSL4. ACSL4 mRNA stability was analyzed by Actinomycin D treatment. RBM15 mRNA level was increased in AMI patients’ serums and H/R-induced AC16 cells. Silencing of RBM15 promoted H/R-mediated AC16 cell viability and inhibited H/R-induced AC16 cell oxidative stress and ferroptosis. Moreover, it was demonstrated that RBM15 knockdown inhibited m6A modification of ACSL4 and suppressed the stability of ACSL4 mRNA. Furthermore, ACSL4 overexpression restored the effects of RNM15 silencing on H/R-induced AC16 cell oxidative injury and ferroptosis. Conclusion RBM15 silencing repressed H/R-induced ferroptosis in human cardiomyocytes through regulating m6A modification of ACSL4. |
| format | Article |
| id | doaj-art-b8027e623c6e4248b1a676f89b2b31e1 |
| institution | DOAJ |
| issn | 1601-5223 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Hereditas |
| spelling | doaj-art-b8027e623c6e4248b1a676f89b2b31e12025-08-20T03:05:29ZengBMCHereditas1601-52232025-07-01162111010.1186/s41065-025-00453-0RBM15 promotes hypoxia/reoxygenation-induced ferroptosis in human cardiomyocytes by mediating m6A modification of ACSL4Yi Cheng0Jiamin Wan1Yingyue Xu2Shasha Liu3Linfeng Li4Jing Zhou5Fuyan Xie6Department of Geriatric Medicine, Bishan Hospital of Chongqing, Bishan Hospital of Chongqing Medical UniversityDepartment of Geriatric Medicine, Bishan Hospital of Chongqing, Bishan Hospital of Chongqing Medical UniversityDepartment of Geriatric Medicine, Bishan Hospital of Chongqing, Bishan Hospital of Chongqing Medical UniversityDepartment of Geriatric Medicine, Bishan Hospital of Chongqing, Bishan Hospital of Chongqing Medical UniversityDepartment of Emergency Medicine, Bishan Hospital of Chongqing, Bishan hospital of Chongqing Medical UniversityDepartment of Geriatric Medicine, Bishan Hospital of Chongqing, Bishan Hospital of Chongqing Medical UniversityDepartment of Geriatric Medicine, Bishan Hospital of Chongqing, Bishan Hospital of Chongqing Medical UniversityAbstract Background Acute myocardial infarction (AMI) refers to the acute necrosis of part of the myocardium caused by persistent and severe myocardial ischemia. The aim of the study was to investigate the effect of RNA binding motif protein 15 (RBM15) and acyl-CoA synthetase long chain family member 4 (ACSL4) on ischemia/reperfusion (I/R)-induced ferroptosis of cardiomyocytes. Methods and results AC16 cells were treated with hypoxia/reoxygenation (H/R) to establish an in vitro myocardial infarction cell model. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot assay were used to determine gene expression. Cell Counting Kit-8 (CCK-8) assay was conducted to investigate cell viability. Ferroptosis level was evaluated by commercial kits. N6-methyladenosine (m6A) level was examined by M6A quantification analysis. RNA immunoprecipitation (RIP) assay, methylated RNA Immunoprecipitation (meRIP) assay and dual-luciferase reporter assay were adopted to verify the combination between RBM15 and ACSL4. ACSL4 mRNA stability was analyzed by Actinomycin D treatment. RBM15 mRNA level was increased in AMI patients’ serums and H/R-induced AC16 cells. Silencing of RBM15 promoted H/R-mediated AC16 cell viability and inhibited H/R-induced AC16 cell oxidative stress and ferroptosis. Moreover, it was demonstrated that RBM15 knockdown inhibited m6A modification of ACSL4 and suppressed the stability of ACSL4 mRNA. Furthermore, ACSL4 overexpression restored the effects of RNM15 silencing on H/R-induced AC16 cell oxidative injury and ferroptosis. Conclusion RBM15 silencing repressed H/R-induced ferroptosis in human cardiomyocytes through regulating m6A modification of ACSL4.https://doi.org/10.1186/s41065-025-00453-0AMIRBM15ACSL4AC16m6A |
| spellingShingle | Yi Cheng Jiamin Wan Yingyue Xu Shasha Liu Linfeng Li Jing Zhou Fuyan Xie RBM15 promotes hypoxia/reoxygenation-induced ferroptosis in human cardiomyocytes by mediating m6A modification of ACSL4 Hereditas AMI RBM15 ACSL4 AC16 m6A |
| title | RBM15 promotes hypoxia/reoxygenation-induced ferroptosis in human cardiomyocytes by mediating m6A modification of ACSL4 |
| title_full | RBM15 promotes hypoxia/reoxygenation-induced ferroptosis in human cardiomyocytes by mediating m6A modification of ACSL4 |
| title_fullStr | RBM15 promotes hypoxia/reoxygenation-induced ferroptosis in human cardiomyocytes by mediating m6A modification of ACSL4 |
| title_full_unstemmed | RBM15 promotes hypoxia/reoxygenation-induced ferroptosis in human cardiomyocytes by mediating m6A modification of ACSL4 |
| title_short | RBM15 promotes hypoxia/reoxygenation-induced ferroptosis in human cardiomyocytes by mediating m6A modification of ACSL4 |
| title_sort | rbm15 promotes hypoxia reoxygenation induced ferroptosis in human cardiomyocytes by mediating m6a modification of acsl4 |
| topic | AMI RBM15 ACSL4 AC16 m6A |
| url | https://doi.org/10.1186/s41065-025-00453-0 |
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