Overexpression of miR-638 attenuated the effects of hypoxia/reoxygenation treatment on cell viability, cell apoptosis and autophagy by targeting ATG5 in the human cardiomyocytes.

Abstract

Myocardial ischemia/reperfusion (I/R) injury largely contributed to the damage of myocardial tissues in patients with coronary disease, which may subsequently lead to heart failure. MicroRNAs (miRNAs) are considered to be involved in the process of myocardial I/R injury. The present study aimed to investigate the in vitro functional role of miR-638 in the myocardial I/R injury in the human cardiomyocytes (HCMs). MTT assay and flow cytometry assay were performed to determine cell viability and apoptosis of HCMs. Real Time-quantitative Polymerase Chain Reaction was used to determine miRNA and mRNA expression levels. The protein levels were determined by Western blot assay. Hypoxia/reoxygenation (H/R) treatment suppressed cell viability, increased cell apoptotic rate and suppressed miR-638 expression in the HCMs. The downregulation of miR-638 suppressed cell viability and induced cell apoptosis in the HCMs. The overexpression of miR-638 attenuated the effects of H/R treatment on the cell viability and cell apoptosis in the HCMs. In addition, miR-638 suppressed the expression of autophagy-related 5 (ATG5) by targeting the 3'untranslated region of ATG5. Enforced expression of ATG5 reversed the effects of miR-638 overexpression on cell viability and cell apoptosis in H/R-treated HCMs. More importantly, H/R treatment promoted autophagy in the HCMs, and this effect was significantly reversed by miR-638 mimic transfection. Our results suggested that the overexpression of miR-638 attenuated the effects of H/R treatment on cell viability, cell apoptosis and autophagy, at least partly by regulating the ATG5 expression in the HCMs.