Critical roles of microRNA-141-3p and CHD8 in hypoxia/reoxygenation-induced cardiomyocyte apoptosis

Bifeng Yao,Deling Yin,Yeshuo Ma,Ting Zhong,Jia Hu,Anna Qin,Xiaoya Wan,Xinbin Zheng,Yu Zhou

doi:10.1186/s13578-020-00384-5

Abstract

BackgroundCardiovascular diseases are currently the leading cause of death in humans. The high mortality of cardiac diseases is associated with myocardial ischemia and reperfusion (I/R). Recent studies have reported that microRNAs (miRNAs) play important roles in cell apoptosis. However, it is not known yet whether miR-141-3p contributes to the regulation of cardiomyocyte apoptosis. It has been well established that in vitro hypoxia/reoxygenation (H/R) model can follow in vivo myocardial I/R injury. This study aimed to investigate the effects of miR-141-3p and CHD8 on cardiomyocyte apoptosis following H/R.ResultsWe found that H/R remarkably reduces the expression of miR-141-3p but enhances CHD8 expression both in mRNA and protein in H9c2 cardiomyocytes. We also found either overexpression of miR-141-3p by transfection of miR-141-3p mimics or inhibition of CHD8 by transfection of small interfering RNA (siRNA) significantly decrease cardiomyocyte apoptosis induced by H/R. Moreover, miR-141-3p interacts with CHD8. Furthermore, miR-141-3p and CHD8 reduce the expression of p21.ConclusionMiR-141-3p and CHD8 play critical roles in cardiomyocyte apoptosis induced by H/R. These studies suggest that miR-141-3p and CHD8 mediated cardiomyocyte apoptosis may offer a novel therapeutic strategy against myocardial I/R injury-induced cardiovascular diseases.

Highlights

Cardiovascular diseases are currently the leading cause of death in humans [1,2,3,4,5]
MiR‐141‐3p is downregulated by hypoxia/reoxygenation (H/R) in H9c2 cardiomyocytes To investigate whether miR-141-3p plays a role in H/R-induced injury in cardiomyocytes
Overexpression of miR‐141‐3p dramatically decreases H/R‐induced H9c2 cardiomyocyte apoptosis To determine whether miR-141-3p contributed to H/R induced cardiomyocyte apoptosis, we examined the alterations of apoptotic marker cleaved caspase-3 (Clcaspase-3) protein and performed flow cytometric analysis in H9c2 cardiomyocytes after transfection with miR-141-3p mimics

Summary

Introduction

Cardiovascular diseases are currently the leading cause of death in humans [1,2,3,4,5]. Our previous studies by RNA sequencing found that a long non-coding RNA is involved in ischemia and reperfusion injury. Previous studies reported that miR-141-3p is associated with glioma cell growth [16], mesenchymal stem cell aging [17], and I/R injury in endothelial cells [18]. The roles and mechanisms of miR141-3p in myocardial I/R injury or in hypoxia/reoxygenation (H/R) in vitro model remain to be elucidated. Recent studies have reported that microRNAs (miRNAs) play important roles in cell apoptosis. It is not known yet whether miR-141-3p contributes to the regulation of cardiomyocyte apoptosis. It has been well established that in vitro hypoxia/reoxygenation (H/R) model can follow in vivo myocardial I/R injury. This study aimed to investigate the effects of miR-141-3p and CHD8 on cardiomyocyte apoptosis following H/R

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