Shen Chuqiao, Chen Xiaoqi, Lin Yixuan, Yang Yan
Department of Pharmacology, School of Basic Medical Science, Anhui Medical University, Hefei, Anhui, 230012, PR China.
Graduate School, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, PR China.
Heliyon. 2024 Jun 5;10(11):e32455. doi: 10.1016/j.heliyon.2024.e32455. eCollection 2024 Jun 15.
Long-time hypoxia induced cardiomyocyte apoptosis is an important mechanism of myocardial ischemia (MI) injury. Interestingly, long noncoding RNA myocardial infarction-associated transcript (LncMIAT) has been involved in the regulation of MI injury; however, the underlying mechanism by which LncMIAT affects the progression of hypoxia-induced cardiomyocyte apoptosis remains unclear. In the present study, hypoxia was found to promote cardiomyocyte apoptosis through an increased expression of LncMIAT . Biological investigations and dual-luciferase gene reporter assay further revealed that LncMIAT was able to bind with miR-708-5p to upregulate the p53-mediated cell death of the cardiomyocytes. Silencing of LncMIAT or overexpression of miR-708-5p led to a significant reduction in p53-mediated cardiomyocyte apoptosis. The methylated RNA immunoprecipitation (MeRIP)-qPCR results showed that hypoxia exerted its effects on LncMIAT through AKLBH5-N-methyladenosine (mA) methylation and therefore hypoxia was shown to trigger HL-1 cardiomyocyte apoptosis via the mA methylation-mediated LncMIAT/miR-708-5p/p53 axis. Silencing of AKLBH5 significantly alleviated the mA methylation-mediated LncMIAT upregulation and p53-mediated cardiomyocyte apoptosis, while promoted miR-708-5p expression. Taken together, the present study highlighted that LncMIAT could act as a key biological target during hypoxia-induced cardiomyocyte apoptosis. In addition, it was shown that hypoxia could promote cardiomyocyte apoptosis through regulation of the mA methylation-mediated LncMIAT/miR-708-5p/p53 signaling axis.
长期缺氧诱导的心肌细胞凋亡是心肌缺血（MI）损伤的重要机制。有趣的是，长链非编码RNA心肌梗死相关转录本（LncMIAT）已参与MI损伤的调控；然而，LncMIAT影响缺氧诱导的心肌细胞凋亡进程的潜在机制仍不清楚。在本研究中，发现缺氧通过增加LncMIAT的表达促进心肌细胞凋亡。生物学研究和双荧光素酶基因报告试验进一步表明，LncMIAT能够与miR-708-5p结合，上调p53介导的心肌细胞死亡。沉默LncMIAT或过表达miR-708-5p可显著减少p53介导的心肌细胞凋亡。甲基化RNA免疫沉淀（MeRIP）-qPCR结果表明，缺氧通过AKLBH5-N-甲基腺苷（mA）甲基化对LncMIAT发挥作用，因此缺氧通过mA甲基化介导的LncMIAT/miR-708-5p/p53轴触发HL-1心肌细胞凋亡。沉默AKLBH5可显著减轻mA甲基化介导的LncMIAT上调和p53介导的心肌细胞凋亡，同时促进miR-708-5p表达。综上所述，本研究强调LncMIAT可能是缺氧诱导心肌细胞凋亡过程中的关键生物学靶点。此外，研究表明缺氧可通过调节mA甲基化介导的LncMIAT/miR-708-5p/p53信号轴促进心肌细胞凋亡。
