miR-25 Promotes Cardiomyocyte Proliferation by Targeting FBXW7

Bei Wang; Mengting Xu; Miaomiao Li; Fujian Wu; Shijun Hu; Xiangbo Chen; Liqun Zhao; Zheyong Huang; Feng Lan; Dong Liu; Yongming Wang

doi:10.1016/j.omtn.2020.01.013

miR-25 Promotes Cardiomyocyte Proliferation by Targeting FBXW7

Mol Ther Nucleic Acids. 2020 Mar 6:19:1299-1308. doi: 10.1016/j.omtn.2020.01.013. Epub 2020 Jan 21.

Authors

Bei Wang¹, Mengting Xu², Miaomiao Li¹, Fujian Wu³, Shijun Hu⁴, Xiangbo Chen⁵, Liqun Zhao⁶, Zheyong Huang⁷, Feng Lan⁸, Dong Liu⁹, Yongming Wang¹⁰

Affiliations

¹ State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China.
² School of Life Sciences, Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China.
³ Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Beijing 100029, China.
⁴ Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Soochow University, Suzhou 215007, China.
⁵ Key Laboratory of Molecular Epigenetics of the Ministry of Education (MOE), Northeast Normal University, Changchun 130024, China; Hangzhou Rongze Biotechnology, Hangzhou 310000, Zhejiang, China.
⁶ Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
⁷ Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
⁸ Beijing Anzhen Hospital, Beijing Institute of Heart Lung and Blood Vessel Disease, Capital Medical University, Beijing 100029, China. Electronic address: fenglan@ccmu.edu.cn.
⁹ School of Life Sciences, Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China. Electronic address: tom@ntu.edu.cn.
¹⁰ State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China; School of Life Sciences, Co-innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China. Electronic address: ymw@fudan.edu.cn.

Abstract

Induction of endogenous cardiomyocyte (CM) proliferation is one of the key strategies for heart regeneration. Increasing evidence points to the potential role of microRNAs (miRNAs) in the regulation of CM proliferation. Here, we used human embryonic stem cell (hESC)-derived CMs (hESC-CMs) as a tool to identify miRNAs that promote CM proliferation. We profiled miRNA expression at an early stage of CM differentiation and identified a list of highly expressed miRNAs. Among these miRNAs, miR-25 was enriched in early-stage hESC-CMs, but its expression decreased over time. Overexpression of miR-25 promoted CM proliferation. RNA sequencing (RNA-seq) analysis revealed that genes related to cell-cycle signal were strongly influenced by miR-25 overexpression. We further showed that miR-25 promoted CM proliferation by targeting FBXW7. Finally, the function of miR-25 in the regulation of CM proliferation was demonstrated in zebrafish. Our study suggested that miR-25 is a promising molecule for heart regeneration.

Keywords: cardiomyocytes; human embryonic stem cell; miR-25; proliferation.