Long noncoding RNA MALAT1 enhances the apoptosis of cardiomyocytes through autophagy modulation.

Abstract

Induction of autophagy promotes cardiomyocyte survival and confers a cardioprotective effect on acute myocardial infarction (AMI). Our previous study showed that knockdown of long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) attenuated myocardial apoptosis in mouse AMI. Herein, this study further investigated whether the mechanisms by which MALAT1 enhanced cardiomyocyte apoptosis involved the autophagy regulation. To address this, cardiomyocytes were isolated from neonatal mice and then stimulated with hypoxia/reoxygenation (H/R) injury to mimic AMI. The cell apoptosis was evaluated using TUNEL staining and Western blot analysis of apoptosis-related proteins. The autophagy level was assessed using GFP-LC3 immunofluorescence and Western blot analysis of autophagy-related proteins. The results showed that H/R injury increased MALAT1 expression. Furthermore, MALAT1 overexpression significantly enhanced apoptosis and regulated autophagy of cardiomyocytes, whereas MALAT1 knockdown exerted the opposite effect. Moreover, rapamycin (an autophagy activator) effectively attenuated the MALAT1-mediated enhancement of cardiomyocyte apoptosis. Overall, our findings demonstrated that the increased MALAT1 expression induced by H/R injury enhances cardiomyocyte apoptosis, at least in part, through autophagy modulation.