MircroRNA-10b Promotes Human Embryonic Stem Cell-Derived Cardiomyocyte Proliferation via Novel Target Gene LATS1

Abstract

Adult mammalian cardiomyocytes (CMs) retain a limited proliferative ability, which is insufficient for the repair of CM loss in ischemic cardiac injury. Regulation of the Hippo signaling pathway to promote endogenous CM proliferation has emerged as a promising strategy for heart regeneration. Previous studies have shown that the microRNA cluster miR302–367 negatively regulates the Hippo pathway, promoting CM proliferation. In this study, we identified another microRNA, miR-10b, that regulates the Hippo pathway and promotes cell proliferation in human embryonic stem cell-derived CMs (hESC-CMs). We observed that miR-10b expression was enriched in the early stage of CMs, but its expression was reduced over time. Overexpression of miR-10b promoted CM proliferation, while knockdown of miR-10b suppressed CM proliferation. Moreover, miR-10b protected CMs against apoptosis. miR-10b functions, in part, by directly targeting LATS1, which is a major component of the Hippo pathway. Our study suggests that miR-10b has promising potential for heart regeneration.