MicroRNA-19a/b family positively regulates cardiomyocyte hypertrophy by targeting atrogin-1 and MuRF-1

ABSTRACT Progressive cardiac hypertrophy due to pathological stimuli such as pressure overload is frequently associated with the development of heart failure, a major cause of morbidity and mortality worldwide. Growing evidence has shown that microRNAs (miRNAs) are extensively involved in the pathogenesis of cardiac hypertrophy. Here, we examined the hypothesis that miR-19a/b family acts as a key regulator of cardiac hypertrophy and apoptosis. Forced overexpression of miR-19a/b was sufficient to induce hypertrophy in rat neonatal cardiomyocytes. Luciferase assays revealed that miR-19a/b directly target the anti-hypertrophic genes atrogin-1 and MuRF-1. The endogenous expressions of the target genes were down-regulated by miR-19a/b. Pro-hypertrophic calcineurin/NFAT signaling was markedly elevated in the presence of miR-19b, and the calcineurin inhibitor CsA and the PKC inhibitor GF10923X significantly attenuated miR-19b-mediated increase in cell size and expression of hypertrophic markers. Furthermore, miR-19b led to increased cell survival through up-regulation of the NFAT target gene encoding α-crystallin-B and repression of the pro-apoptotic gene Bim in ER stress conditions. Taken together, our results demonstrate that miR-19a/b family regulates phenotypes of cardiomyocytes via suppression of multiple direct target genes.
Source: BJ Gene - Category: Biochemistry Authors: Tags: BJ Signal Source Type: research