Inhibition of Smurf2 translation by miR-322/503 protects from ischemia reperfusion injury by modulating EZH2/Akt/GSK3β signaling

BACKGROUND: myocardial ischemia/reperfusion (I/R) is a common and lethal disease that threatens people's life worldwide. The underlying mechanisms are under intensive study and yet remain unclear. Here, we explored the function of miR-322/503 in myocardial I/R injury. METHODS: We used isolated rat perfused heart as an in vivo model and H9c2 cells subjected with the oxygen and glucose deprivation followed by reperfusion (OGD/R) as in vitro model to study myocardial I/R injury. TTC staining was used to measure the infarct size and TUNEL staining was used to examine apoptosis. qRT-PCR and western blot were used to determine expression levels of miR-322/503, Smurf2, EZH2, p-Akt, p-GSK3β. RESULTS: Overexpression of miR-322/503 decreased infarct size, inhibited cell apoptosis and promoted cell proliferation through up-regualtion of p-Akt and p-GSK3β. Thus, the expression of miR-322/503 was reduced during I/R process. On the molecular level, miR-322/503 directly bound Smurf2 mRNA and suppressed its translation. ...