{"title":"在hg诱导的H9C2细胞中，METTL14通过介导NRG4的m6A甲基化阻碍DCM进展。","authors":"Ting Li, Mingcheng Fang, Zhiyong Wu","doi":"10.1007/s12033-025-01507-4","DOIUrl":null,"url":null,"abstract":"<p><p>Diabetic cardiomyopathy (DCM) is a common form of cardiomyopathy that affects the cardiac muscle. It can lead to heart failure and threaten the life of human. Neuregulin 4 (NRG4) is a novel adipose factor released from brown adipose tissues and is considered to play an important role in metabolism, and affects the diabetic cardiomyopathy. N6-Methyladenosine (m6A) modification has been implicated in many bioprocesses. So we aim to explore the role of methyltransferase 14 (METTL14) and NRG4 in the progression of DCM. The high-glucose (HG) could increase the expression of NRG4. In HG-induced H9C2 cells, the up-regulated NRG4 promoted the cell proliferation and GSH levels, and suppressed the cell apoptosis, inflammation factors (IL-1β and IL-6), and Fe<sup>2+</sup> and ROS levels. The RMbase database, SRAMP website, and RMvar database predicted that NRG4 had m6A modification site. Western blot assay demonstrated that OE-METTL14 promoted NRG4 expression. METTL3 could bind to NRG4. Besides, METTL14 and IGF2BP1 positively regulated NRG4 by increasing its mRNA stability. In HG-induced H9C2 cells, METTL14 promoted the NRG4 levels and cell proliferation and retarded the cell apoptosis, inflammation and ferroptosis via facilitating expression of NRG4. Besides, the METTL14 overexpression could increase the expression of nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in HG-induced H9C2 cells. METTL14 curbs the progression of DCM via enhancing the m6A methylation of NRG4 in HG-induced H9C2 cells, which can help extend our understanding on the epigenetic regulation of ferroptosis in DCM progression.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":""},"PeriodicalIF":2.5000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"METTL14 Hinders DCM Progression via Mediating the m6A Methylation of NRG4 in HG-Induced H9C2 Cells.\",\"authors\":\"Ting Li, Mingcheng Fang, Zhiyong Wu\",\"doi\":\"10.1007/s12033-025-01507-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Diabetic cardiomyopathy (DCM) is a common form of cardiomyopathy that affects the cardiac muscle. It can lead to heart failure and threaten the life of human. Neuregulin 4 (NRG4) is a novel adipose factor released from brown adipose tissues and is considered to play an important role in metabolism, and affects the diabetic cardiomyopathy. N6-Methyladenosine (m6A) modification has been implicated in many bioprocesses. So we aim to explore the role of methyltransferase 14 (METTL14) and NRG4 in the progression of DCM. The high-glucose (HG) could increase the expression of NRG4. In HG-induced H9C2 cells, the up-regulated NRG4 promoted the cell proliferation and GSH levels, and suppressed the cell apoptosis, inflammation factors (IL-1β and IL-6), and Fe<sup>2+</sup> and ROS levels. The RMbase database, SRAMP website, and RMvar database predicted that NRG4 had m6A modification site. Western blot assay demonstrated that OE-METTL14 promoted NRG4 expression. METTL3 could bind to NRG4. Besides, METTL14 and IGF2BP1 positively regulated NRG4 by increasing its mRNA stability. In HG-induced H9C2 cells, METTL14 promoted the NRG4 levels and cell proliferation and retarded the cell apoptosis, inflammation and ferroptosis via facilitating expression of NRG4. Besides, the METTL14 overexpression could increase the expression of nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in HG-induced H9C2 cells. METTL14 curbs the progression of DCM via enhancing the m6A methylation of NRG4 in HG-induced H9C2 cells, which can help extend our understanding on the epigenetic regulation of ferroptosis in DCM progression.</p>\",\"PeriodicalId\":18865,\"journal\":{\"name\":\"Molecular Biotechnology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Biotechnology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12033-025-01507-4\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Biotechnology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12033-025-01507-4","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
METTL14 Hinders DCM Progression via Mediating the m6A Methylation of NRG4 in HG-Induced H9C2 Cells.
Diabetic cardiomyopathy (DCM) is a common form of cardiomyopathy that affects the cardiac muscle. It can lead to heart failure and threaten the life of human. Neuregulin 4 (NRG4) is a novel adipose factor released from brown adipose tissues and is considered to play an important role in metabolism, and affects the diabetic cardiomyopathy. N6-Methyladenosine (m6A) modification has been implicated in many bioprocesses. So we aim to explore the role of methyltransferase 14 (METTL14) and NRG4 in the progression of DCM. The high-glucose (HG) could increase the expression of NRG4. In HG-induced H9C2 cells, the up-regulated NRG4 promoted the cell proliferation and GSH levels, and suppressed the cell apoptosis, inflammation factors (IL-1β and IL-6), and Fe2+ and ROS levels. The RMbase database, SRAMP website, and RMvar database predicted that NRG4 had m6A modification site. Western blot assay demonstrated that OE-METTL14 promoted NRG4 expression. METTL3 could bind to NRG4. Besides, METTL14 and IGF2BP1 positively regulated NRG4 by increasing its mRNA stability. In HG-induced H9C2 cells, METTL14 promoted the NRG4 levels and cell proliferation and retarded the cell apoptosis, inflammation and ferroptosis via facilitating expression of NRG4. Besides, the METTL14 overexpression could increase the expression of nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in HG-induced H9C2 cells. METTL14 curbs the progression of DCM via enhancing the m6A methylation of NRG4 in HG-induced H9C2 cells, which can help extend our understanding on the epigenetic regulation of ferroptosis in DCM progression.
期刊介绍：
Molecular Biotechnology publishes original research papers on the application of molecular biology to both basic and applied research in the field of biotechnology. Particular areas of interest include the following: stability and expression of cloned gene products, cell transformation, gene cloning systems and the production of recombinant proteins, protein purification and analysis, transgenic species, developmental biology, mutation analysis, the applications of DNA fingerprinting, RNA interference, and PCR technology, microarray technology, proteomics, mass spectrometry, bioinformatics, plant molecular biology, microbial genetics, gene probes and the diagnosis of disease, pharmaceutical and health care products, therapeutic agents, vaccines, gene targeting, gene therapy, stem cell technology and tissue engineering, antisense technology, protein engineering and enzyme technology, monoclonal antibodies, glycobiology and glycomics, and agricultural biotechnology.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
