Theranostics 2017; 7(7):1953-1965. doi:10.7150/thno.16478

Research Paper

Neonatal Heart-Enriched miR-708 Promotes Proliferation and Stress Resistance of Cardiomyocytes in Rodents

Shengqiong Deng1,2*, Qian Zhao1*, Chuyi Zhang1*, Lixiao Zhen1, Cuicui Liu1, Guangxue Wang1, Lin Zhang1, Luer Bao1, Ying Lu1, Lingyu Meng1,3, Jinhui Lü1, Ping Yu1, Xin Lin1, Yuzhen Zhang1, Yi-Han Chen1, Huimin Fan1, William C. Cho4, Zhongmin Liu1✉, Zuoren Yu1,3✉

1. Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, Translational Medical Center for Stem Cell Therapy, East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai 200120, China;
2. Shanghai Gongli Hospital, the Second Military Medical University, Shanghai 200120, China
3. East Hospital, Dalian Medical University, Dalian, China
4. Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China.
* Equal contribution to this work

Abstract

Adult heart has limited potential for regeneration after pathological injury due to the limited cell proliferation of cardiomyocytes and the quiescent status of progenitor cells. As such, induction of cell-cycle reentry of cardiomyocytes is one of the key strategies for regeneration of damaged heart. In this study, a subset of miRNAs including miR-708 were identified to be much more abundant in the embryonic and neonatal cardiomyocytes than that in adult rodents. Overexpression of miR-708 promoted cellular proliferation of H9C2 cells or primary cardiomyocytes from neonatal rats or mice in vitro. Lipid nanoparticle delivery of miR-708 promoted myocardial regeneration and heart function recovery in vivo. In addition, miR-708 protected cardiomyocytes against stress-induced apoptosis under hypoxia or isoproterenol treatments. miR-708 inhibited the expression of MAPK14, which has been demonstrated arresting the cell cycle in cardiomyocytes. The cell proliferation-promoting function of miR-708 was dependent at least partly on the expression of MAPK14. These findings strengthen the potential of applying miRNAs to reconstitute lost cardiomyocytes in injured hearts, and may provide a novel miRNA candidate for promoting heart regeneration.

Keywords: miR-708, cardiomyocytes, heart regeneration, MAPK14.

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How to cite this article:
Deng S, Zhao Q, Zhang C, Zhen L, Liu C, Wang G, Zhang L, Bao L, Lu Y, Meng L, Lü J, Yu P, Lin X, Zhang Y, Chen YH, Fan H, Cho WC, Liu Z, Yu Z. Neonatal Heart-Enriched miR-708 Promotes Proliferation and Stress Resistance of Cardiomyocytes in Rodents. Theranostics 2017; 7(7):1953-1965. doi:10.7150/thno.16478. Available from http://www.thno.org/v07p1953.htm