miR-124 inhibits cardiomyocyte apoptosis in myocardial ischaemia-reperfusion injury by activating mitochondrial calcium uniporter regulator 1

Mitochondria-mediated apoptosis is the primary cause of cardiomyocyte death. Therefore, mitochondria are a key target for treating myocardial injury. Mitochondrial calcium uniporter regulator 1 (MCUR1)-mediated mitochondrial calcium homeostasis markedly promotes cell proliferation and resistance to apoptosis. However, whether MCUR1 is involved in regulation of cardiomyocyte apoptosis during myocardial ischaemia-reperfusion remains unknown. microRNA-124 (miR-124) is upregulated in cardiovascular disease, suggesting a key role for miR-124 in the cardiovascular system. Whether miR-124 affects cardiomyocyte apoptosis and myocardial infarction is not well understood. Western blot showed that miR-124 and MCUR1 were upregulated in cardiomyocyte apoptosis induced by hydrogen peroxide (H2O2). Flow cytometry assay of cell apoptosis showed that miR-124 inhibited cardiomyocyte apoptosis by activating MCUR1 following H2O2 treatment. The dual-luciferase reporter assay confirmed binding of miR-124 to MCUR1 3 & PRIME;-UTR and subsequent activation of MCUR1. FISH assay revealed the entry of miR-124 into the cell nucleus. Therefore, MCUR1 was identified as a novel target of miR-124, and it was shown that the miR-124-MCUR1 axis modulated cardiomyocyte apoptosis induced by H2O2 in vitro. The results indicated induced expression of miR-124 during acute myocardial infarction and its transport to the nucleus. In the nucleus, miR-124 transcriptionally activated MCUR1 by binding to its enhancers. These findings reveal a role of miR-124 as a biomarker for myocardial injury and infarction.

Automated summary

Mitochondria-mediated apoptosis is the primary cause of cardiomyocyte death. MCUR1 and miR-124 play important roles in regulating cardiomyocyte apoptosis. This study shows that miR-124 can inhibit cardiomyocyte apoptosis by activating MCUR1, suggesting their potential as biomarkers for myocardial injury and infarction.