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

BACKGROUND: This 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. METHODS: H9c2 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. RESULTS: The 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. CONCLUSIONS: In conclusion, increasing the expression of miR-194 can alleviate CH by targeting can and inhibiting the CnA/NFATc2 pathway.