MiR-625-5p Inhibits Cardiac Hypertrophy Through Targeting STAT3 and CaMKII

Abstract

Cardiac hypertrophy is an adaptive cardiac response to heart stress. Sustained cardiac hypertrophy indicates higher risk of heart failure. Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been proved to be a key regulator of cardiac hypertrophy, but its mechanism remains largely unknown. Our study proposed to explore the regulatory mechanism of CaMKII in cardiac hypertrophy. We validated that CaMKII was upregulated in cardiac hypertrophy models in vivo and in vitro and that knockdown of CaMKII attenuated Ang II–induced cardiac hypertrophy in vitro. Furthermore, we demonstrated that signal transducer and activator of transcription 3 (STAT3) was highly expressed in cardiac hypertrophy and could stimulate the transactivation of CaMKII. Moreover, we predicted through TargetScan and confirmed that miR-625-5p targeted and inhibited STAT3 so as to reduce the expression of CaMKII. Interestingly, we also found that miR-625-5p directly targeted CaMKII and inhibited its expression. Rescue assays suggested that miR-625-5p attenuated Ang II–induced cardiac hypertrophy through CaMKII/STAT3. Consequently, this study elucidated that miR-625-5p inhibited cardiac hypertrophy through targeting STAT3 and CaMKII, suggesting miR-625-5p as a novel negative regulator of cardiac hypertrophy.

Graphical Abstract

Color images are available online.