Hypoxia Triggers Cardiomyocyte Apoptosis Via Regulating the MA Methylation-mediated LncMIAT/miR-708-5p/p53 Axis

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Jul 4

PMID 38961902

Authors

Chuqiao Shen

Xiaoqi Chen

Yixuan Lin

Yan Yang

Affiliations

Soon will be listed here.

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 . 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.

Citing Articles

The potential value of microRNA-409-5p-mediated negative regulation of USP7 in the diagnosis and treatment of acute myocardial infarction.

Fu X, Zhang X, Wang L, Zhang J, Li W, Qin S BMC Cardiovasc Disord. 2025; 25(1):167.

PMID: 40057674 PMC: 11890518. DOI: 10.1186/s12872-025-04590-2.

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