Wang Bei, Xu Mengting, Li Miaomiao, Wu Fujian, Hu Shijun, Chen Xiangbo, Zhao Liqun, Huang Zheyong, Lan Feng, Liu Dong, Wang Yongming
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.
Mol Ther Nucleic Acids. 2020 Mar 6;19:1299-1308. doi: 10.1016/j.omtn.2020.01.013. Epub 2020 Jan 21.
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.
诱导内源性心肌细胞（CM）增殖是心脏再生的关键策略之一。越来越多的证据表明，微小RNA（miRNA）在调节CM增殖中具有潜在作用。在这里，我们使用人胚胎干细胞（hESC）衍生的CM（hESC-CM）作为工具来鉴定促进CM增殖的miRNA。我们在CM分化的早期阶段分析了miRNA表达，并确定了一系列高表达的miRNA。在这些miRNA中，miR-25在早期hESC-CM中富集，但其表达随时间下降。miR-25的过表达促进了CM增殖。RNA测序（RNA-seq）分析表明，与细胞周期信号相关的基因受到miR-25过表达的强烈影响。我们进一步表明，miR-25通过靶向FBXW7促进CM增殖。最后，在斑马鱼中证明了miR-25在调节CM增殖中的功能。我们的研究表明，miR-25是心脏再生的一个有前景的分子。
