METTL14-mediated m6A methylation of pri-miR-5099 to facilitate cardiomyocyte pyroptosis in myocardial infarction

被引：0
作者：
Yu, Hang [1 ,2 ]
Li, Qing-sui [1 ,2 ]
Guo, Jun-nan [3 ]
Zhang, Zhen [1 ,2 ]
Lang, Xian-zhi [1 ,2 ]
Liu, Yi-ning [1 ,2 ]
Qin, Long [1 ,2 ]
Su, Xu [1 ,2 ]
Zhang, Qing-wei [1 ,2 ]
Xue, Ya-dong [1 ,2 ]
Gong, Li-ling [1 ,2 ]
Xu, Ning [1 ,2 ]
Li, Ming [1 ,2 ]
Zhao, Wen-shuang [1 ,2 ]
Zhao, Xing-miao [1 ,2 ]
Zhang, Wan-yu [1 ,2 ]
Yao, Yi-jing [1 ,2 ]
Chen, Xi-ming [1 ,2 ]
Zhang, Zhen [1 ,2 ]
Li, Wei [1 ,2 ]
Wang, Han-xiang [1 ,2 ]
Cai, Ben-zhi [1 ,2 ,4 ,5 ]
Li, Jia-min [1 ,2 ,4 ,5 ]
Wang, Ning [1 ,2 ,4 ,5 ]
机构：
[1] Harbin Med Univ, Affiliated Hosp 2, Dept Pharm, Harbin 150081, Peoples R China
[2] Harbin Med Univ, Coll Pharm, Dept Pharmacol, State Key Lab Frigid Zone Cardiovasc Dis SKLFZCD, Harbin 150081, Peoples R China
[3] Harbin Med Univ, Dept Thorac Surg, Canc Hosp, Harbin 150040, Peoples R China
[4] Chinese Acad Med Sci, Res Unit Noninfect Chron Dis Frigid Zone 2019RU070, Harbin 150081, Peoples R China
[5] Harbin Med Univ, Heilongjiang Acad Med Sci, Northern Translat Med Res & Cooperat Ctr, Harbin 150080, Peoples R China
来源：
ACTA PHARMACOLOGICA SINICA | 2025年
基金：
中国国家自然科学基金; 中国博士后科学基金;
关键词：
myocardial infarction; m(6)A modification; METTL14; miRNA-5099-3p; cardiomyocyte pyroptosis; ELF1; CELL-DEATH; N-6-METHYLADENOSINE; TRANSCRIPTION; METTL14; EXPRESSION; CARCINOMA; CLEAVAGE; PROMOTE; REPAIR; ELF-1;
D O I：
10.1038/s41401-025-01485-y
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
N-6-methyladenosine (m(6)A) modification is an important mechanism in microRNA processing and maturation. Previous studies show the involvement of pri-miRNA methylation in regulating the occurrence and development of tumor-related diseases. In this study, we investigated the role of its aberrant regulation in cardiac diseases. Myocardial infarction (MI) mouse were established by ligation of the left anterior descending branch of the coronary artery. We showed that the expression of methyltransferase 14 (METTL14) was significantly increased in myocardium of MI mice. We demonstrated that METTL14 methylated the primary transcript miRNA (pri-miR-5099), promoting the recognition by DiGeorge critical region 8 (DGCR8) and the maturation processing of pri-miR-5099. Mature microRNA-5099-3p (miR-5099-3p) inhibited the expression of E74 like ETS transcription factor 1 (ELF1), which transcriptionally regulated pyroptosis factors such as acysteinyl aspartate-specific proteinase 1 (caspase-1) and gasdermin D (GSDMD), ultimately leading to cardiomyocyte pyroptosis. This study reveals that myocardial infarction-induced miR-5099-3p excessive maturation via m(6)A modification promotes the development and progression of cardiomyocyte pyroptosis.
引用
收藏
页码：1639 / 1651
页数：13
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