MicroRNA-494 suppresses hypoxia/reoxygenation-induced cardiomyocyte apoptosis and autophagy via the PI3K/AKT/mTOR signaling pathway by targeting SIRT1

Acute myocardial infarction can be caused by ischemia/reperfusion (I/R) injury; however, the mechanism underlying I/R is not completely understood. The present study investigated the functions and mechanisms underlying microRNA (miR)-494 in I/R-induced cardiomyocyte apoptosis and autophagy. Hypoxia/reoxygenation (H/R)-treated H9c2 rat myocardial cells were used as an in vitro I/R injury model. Apoptosis and autophagy were analyzed by Cell Counting Kit-8 assay, Lactic dehydrogenase and superoxide dismutase assay, flow cytometry, TUNEL staining and western blotting. Reverse transcription-quantitative PCR demonstrated that, H9c2 cells treated with 12 h hypoxia and 3 h reoxygenation displayed significantly downregulated miR-494 expression levels compared with control cells. Compared with the corresponding negative control (NC) groups, miR-494 mimic reduced H/R-induced cell apoptosis and autophagy, whereas miR-494 inhibitor displayed the opposite effects. Silent information regulator 1 (SIRT1) was identified as a target gene of miR-494. Furthermore, miR-494 inhibitor-mediated effects on H/R-induced cardiomyocyte apoptosis and autophagy were partially reversed by SIRT1 knockdown. Moreover, compared with si-NC, SIRT1 knockdown significantly increased the phosphorylation levels of PI3K, AKT and mTOR in H/R-treated and miR-494 inhibitor-transfected H9c2 cells. Collectively, the results indicated that miR-494 served a protective role against H/R-induced cardiomyocyte apoptosis and autophagy by directly targeting SIRT1, suggesting that miR-494 may serve as a novel therapeutic target for myocardial I/R injury.