miR-25 Promotes Cardiomyocyte Proliferation by Targeting FBXW7
miR-25 Promotes Cardiomyocyte Proliferation by Targeting FBXW7
复制标题
miR-25 通过靶向 FBXW7 促进心肌细胞增殖。
DOI：
10.1016/j.omtn.2020.01.013
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发表时间：
2020-03-06
影响因子：
8.8
通讯作者：
Wang, Yongming
中科院分区：
文献类型：
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作者：
Wang, Bei;Xu, Mengting;Wang, Yongming
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microRNAs （miRNAs）在调节CM增殖中的潜在作用。在这里，我们使用人胚胎干细胞（hESC）来源的CMs （hESC-CMs）作为鉴定促进CM增殖的mirna的工具。我们分析了CM分化早期的miRNA表达，并鉴定了一系列高表达的miRNA。在这些mirna中，miR-25在早期hESC-CMs中富集，但其表达随着时间的推移而降低。过表达miR-25促进CM增殖。RNA测序（RNA-seq）分析显示，与细胞周期信号相关的基因受到miR-25过表达的强烈影响。我们进一步发现miR-25通过靶向FBXW7促进CM增殖。最后，在斑马鱼中证实了miR-25调控CM增殖的功能。我们的研究表明，miR-25是一种很有前途的心脏再生分子。
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.