The mechanism of miR-23a in regulating myocardial cell apoptosis through targeting FoxO3.

Abstract

Myocardial cell apoptosis represents important pathologic basis of ischemia-reperfusion injury (I/R). MiR-23a is related to myocardial hypertrophy and cardiac remodeling by regulating myocardial cell growth and apoptosis. This study intended to observe the regulating effect of miR-23a in myocardial cell and related target, and investigate its clinical significance to I/R injury. The rats were divided into sham group and myocardial I/R group. Myocardial cell cycle and miR-23a expression were tested. H2O2 was applied to treat H9c2 rat myocardial cell to simulate oxidative stress during I/R. The cells were divided into blank group, NC group, miR-23a mimic group, H2O2 group, and miR-23a + H2O2 group. ROS content and cell apoptosis were detected by flow cytometry. MiR-23a, FoxO3a, and BIM gene expression were determined by qRT-PCR. FoxO3a and BIM protein levels were measured by Western blot. Compared with sham group, myocardial apoptosis increased, while miR-23a expression was significantly downregulated in I/R group. H2O2 treatment markedly increased ROS levels in H9c2 cells and elevated apoptosis. The overexpression of mMiR-23a effectively reduced cell apoptosis induced by H2O2 treatment. H2O2 treatment significantly decreased miR-23a expression, while markedly elevated the levels of FoxO3a and BIM. The overexpression of miR-23a apparently impeded the induction of FoxO3a and BIM by H2O2. The downregulation of miR-23a plays a negative role in oxidative stress and cell apoptosis induced by I/R. The overexpression of miR-23a is of significance to alleviate cell apoptosis through inhibiting FoxO3a and downstream target BIM expression.