MicroRNA-194 inhibits isoproterenol-induced chronic cardiac hypertrophy via targeting CnA/NFATc2 signaling in H9c2 cells

BackgroundThis study explored the effects of microRNA(miR)-194 on chronic cardiac hypertrophy (CH) induced by isoproterenol (ISO). The potential mechanism through regulation of the calcineurin A (CnA)/nuclear factor of activated T cells (NFAT) c2 pathway was investigated in the rat cardiomyoblast cell line H9c2. MethodsH9c2 cells were treated with ISO to induce cardiomyocyte hypertrophy to simulate CH in vitro. The cell surface area was assessed by phalloidin staining. The expression of miR-194, CnA mRNA, and CnA protein were assessed. Furthermore, the cellular localization of the NFATc2 protein after induction of CH was detected. The relationship between miR-194 and the CnA mRNA 3'-untranslated region (UTR) was verified by dual luciferase report assays. By constructing cardiomyocyte cell models with low expression of miR-194 and/or CnA, the effects of miR-194 and CnA on the localization of the NFATc2 protein and cell hypertrophy was investigated. Rescue experiments were conducted to analyze whether overexpression of miR-194 could alleviate the cell hypertrophy induced by ISO. ResultsThe results demonstrated that induction with ISO significantly increased the surface area of H9c2 cells. After induction, the expression of miR-194 decreased, while both CnA mRNA and protein expression increased. Furthermore, the nuclear translocation of NFATc2 was obvious. MiR-194 bound to the 3'-UTR of CnA mRNA and inhibited CnA protein expression. Inhibition of miR-194 expression activated NFATc2 protein expression and increased the H9c2 cell surface area. After CnA expression was disturbed, hypertrophy induced by miR-194 down-regulation was blocked. In addition, overexpression of miR-194 significantly alleviated cell hypertrophy and activation of the CnA/NFATc2 pathway caused by ISO. ConclusionsIn conclusion, increasing the expression of miR-194 can alleviate CH by targeting can and inhibiting the CnA/NFATc2 pathway.