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Hypoxia triggers cardiomyocyte apoptosis via regulating the m6A methylation-mediated LncMIAT/miR-708-5p/p53 axis

Hypoxia triggers cardiomyocyte apoptosis via regulating the m6A methylation-mediated LncMIAT/miR-708-5p/p53 axis

Authors :
Chuqiao Shen
Xiaoqi Chen
Yixuan Lin
Yan Yang
Source :
Heliyon, Vol 10, Iss 11, Pp e32455- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

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 in vitro. 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-N6-methyladenosine (m6A) methylation and therefore hypoxia was shown to trigger HL-1 cardiomyocyte apoptosis via the m6A methylation-mediated LncMIAT/miR-708-5p/p53 axis. Silencing of AKLBH5 significantly alleviated the m6A 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 m6A methylation-mediated LncMIAT/miR-708-5p/p53 signaling axis.

Details

Language :
English
ISSN :
24058440
Volume :
10
Issue :
11
Database :
Directory of Open Access Journals
Journal :
Heliyon
Publication Type :
Academic Journal
Accession number :
edsdoj.b1e2bb266fc4a9cb7387577ef44ee00
Document Type :
article
Full Text :
https://doi.org/10.1016/j.heliyon.2024.e32455