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 . 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.

中文翻译：

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miR-25 通过靶向 FBXW7 促进心肌细胞增殖


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 microRNA (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) 作为工具来识别促进 CM 增殖的 miRNA。我们对 CM 分化早期阶段的 miRNA 表达进行了分析，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，但其表达随着时间的推移而下降。 miR-25 的过度表达促进 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 通过靶向促进 CM 增殖。最后，在斑马鱼中证实了 miR-25 在调节 CM 增殖中的功能。我们的研究表明 miR-25 是一种有前途的心脏再生分子。