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

Yifang Xie; Qiaozi Wang; Ning Gao; Fujian Wu; Feng Lan; Feng Zhang; Li Jin; Zheyong Huang; Junbo Ge; Hongyan Wang; Yongming Wang

doi:10.1016/j.omtn.2019.11.026

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

Mol Ther Nucleic Acids. 2020 Mar 6:19:437-445. doi: 10.1016/j.omtn.2019.11.026. Epub 2019 Nov 29.

Authors

Yifang Xie¹, Qiaozi Wang², Ning Gao³, Fujian Wu⁴, Feng Lan⁴, Feng Zhang⁵, Li Jin³, Zheyong Huang², Junbo Ge⁶, Hongyan Wang⁷, Yongming Wang⁸

Affiliations

¹ Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering at School of Life Sciences, Institute of Reproduction and Development, Fudan University, Shanghai 200011, China.
² Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China.
³ State Key Laboratory of Genetic Engineering and School of Life Sciences, Fudan University, Shanghai 200438, China.
⁴ Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Beijing 100029, China.
⁵ Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering at School of Life Sciences, Institute of Reproduction and Development, Fudan University, Shanghai 200011, China.
⁶ Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China. Electronic address: junboge@126.com.
⁷ Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China; Obstetrics and Gynecology Hospital, State Key Laboratory of Genetic Engineering at School of Life Sciences, Institute of Reproduction and Development, Fudan University, Shanghai 200011, China; Key Laboratory of Reproduction Regulation of NPFPC, Collaborative Innovation Center of Genetics and Development, Fudan University, Shanghai 200032, China; Children's Hospital of Fudan University, Shanghai 201102, China. Electronic address: wanghy@fudan.edu.cn.
⁸ Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China; State Key Laboratory of Genetic Engineering and School of Life Sciences, Fudan University, Shanghai 200438, China. Electronic address: ymw@fudan.edu.cn.

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.

Keywords: Hippo pathway; cardiomyocytes; human embryonic stem cells; miR-10b; proliferation.