School of Agriculture, Ningxia University, Helan Mountain West Road 489, Yinchuan 750021, China.
Genes (Basel). 2022 May 26;13(6):947. doi: 10.3390/genes13060947.
Non-coding RNAs, especially microRNAs (miRNAs), play an important role in skeletal muscle growth and development. miR-377 regulates many basic biological processes and plays a key role in tumor cell proliferation, migration and apoptosis. Nevertheless, the function of miR-377 during skeletal muscle development and how it regulates skeletal muscle satellite cells (SMSCs) remains unclear. In the present study, we proposed to elucidate the regulatory mechanism of miR-377 in the proliferation and differentiation of bovine primary SMSCs. Our results showed that miR-377 can significantly inhibit the proliferation of SMSCs. In addition, we found that miR-377 can reduce myotube formation and restrain skeletal myogenic differentiation. Moreover, the results obtained from the biosynthesis and dual luciferase experiments showed that FHL2 was the target gene of miR-377. We further probed the function of FHL2 in muscle development and found that FHL2 silencing significantly suppressed the proliferation and differentiation of SMSCS, which is contrary to the role of miR-377. Furthermore, FHL2 interacts with Dishevelled-2 (Dvl2) to enable Wnt/β-catenin signaling pathway, consequently regulating skeletal muscle development. miR-377 negatively regulates the Wnt/β-catenin signaling pathway by targeting FHL2-mediated Dvl2. Overall, these findings demonstrated that miR-377 regulates the bovine SMSCs proliferation and differentiation by targeting FHL2 and attenuating the Wnt/β-catenin signaling pathway.
非编码 RNA，特别是 microRNAs（miRNAs），在骨骼肌的生长和发育中发挥着重要作用。miR-377 调节许多基本的生物过程，在肿瘤细胞的增殖、迁移和凋亡中起着关键作用。然而，miR-377 在骨骼肌发育过程中的功能以及它如何调节骨骼肌卫星细胞（SMSCs）尚不清楚。在本研究中，我们提出了阐明 miR-377 在牛原代 SMSCs 增殖和分化中的调节机制的研究方案。研究结果表明，miR-377 可以显著抑制 SMSCs 的增殖。此外，我们发现 miR-377 可以减少肌管形成并抑制骨骼肌的成肌分化。此外，生物合成和双荧光素酶实验的结果表明，FHL2 是 miR-377 的靶基因。我们进一步研究了 FHL2 在肌肉发育中的功能，发现 FHL2 沉默显著抑制了 SMSCS 的增殖和分化，这与 miR-377 的作用相反。此外，FHL2 与 Dvl2 相互作用以激活 Wnt/β-catenin 信号通路，从而调节骨骼肌的发育。miR-377 通过靶向 FHL2 介导的 Dvl2 负调控 Wnt/β-catenin 信号通路。综上所述，这些发现表明 miR-377 通过靶向 FHL2 并抑制 Wnt/β-catenin 信号通路来调节牛 SMSCs 的增殖和分化。
