Inhibition of microRNA-101 attenuates hypoxia/reoxygenation-induced apoptosis through induction of autophagy in H9c2 cardiomyocytes

Abstract

Autophagy is a cellular self-catabolic process responsible for the degradation of proteins and organelles. Autophagy is able to promote cell survival in response to stress, and increased autophagy amongst cardiomyocytes has been identified in conditions of heart failure, starvation and ischemia/reperfusion. However, the detailed regulatory mechanisms underlying autophagy in heart disease have remained elusive. MicroRNAs (miRNAs) have been implicated in the regulation of autophagy in cells under stress. In the present study, the protective effect of miRNA (miR)-101 on hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis was investigated. It was revealed that H/R induced apoptosis in H9c2 cardiomyocytes, accompanied by a downregulation of miR-101 expression. Further investigation identified Ras-related protein Rab-5A (RAB5A) as a direct target of miR-101. RAB5A was previously reported to be involved in autophagy; therefore, the present study further focused on the role of miR-101 in the regulation of autophagy under H/R and found that the inhibition of miR-101 attenuated H/R-induced apoptosis, at least partially, via the induction of autophagy. In conclusion, the results of the present study revealed a beneficial effect of miR-101 inhibition on H/R-induced apoptosis in cardiomyocytes, indicating that miR-101 inhibition may present a potential therapeutic agent in the treatment or prevention of heart diseases.