MicroRNA-101b attenuates cardiomyocyte hypertrophy by inhibiting protein kinase C epsilon signaling.

Abstract

Previously, a surgical regression model identified microRNA-101b (miR-101b) as a potential inhibitor of cardiac hypertrophy. Here, we investigated the antihypertrophic mechanism of miR-101b using neonatal rat ventricular myocytes. miR-101b markedly suppressed agonist-induced cardiac hypertrophy as shown by cell size and fetal gene expression. By systems biology approaches, we identified protein kinase C epsilon (PKC epsilon) as the major target of miR-101b. Our results from qRT-PCR, western blot, and luciferase reporter assays confirm that PKC epsilon is a direct target of miR-101b. In addition, we found that effectors downstream of PKCe (p-AKT, p-ERK1/2, p-NFAT, and p-GSK3 beta) are also affected by miR-101b. Our study reveals a novel inhibitory mechanism for miR-101b as a negative regulator of cardiac hypertrophy.