Molecular Therapy - Nucleic Acids ( IF 7.032 ) Pub Date : 2020-01-21 , DOI: 10.1016/j.omtn.2020.01.013 Bei Wang,Mengting Xu,Miaomiao Li,Fujian Wu,Shijun Hu,Xiangbo Chen,Liqun Zhao,Zheyong Huang,Feng Lan,Dong Liu,Yongming Wang
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 promotes CM proliferation. We profiled miRNA expression at 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-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.