miR-9-5p promotes myogenic differentiation via the Dlx3/Myf5 axis.
miR-9-5p promotes myogenic differentiation via the Dlx3/Myf5 axis.
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miR-9-5p 通过 Dlx3/Myf5 轴促进肌原性分化
DOI：
10.7717/peerj.13360
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发表时间：
2022
期刊：
影响因子：
2.7
通讯作者：
Wang, Yixiang
中科院分区：
文献类型：
--
作者：
Dong, Liying;Wang, Meng;Gao, Xiaolei;Zheng, Xuan;Zhang, Yixin;Sun, Liangjie;Zhao, Na;Ding, Chong;Ma, Zeyun;Wang, Yixiang
MicroRNAs在肌源性分化中发挥重要作用，它们与靶基因结合并调节肌肉的形成。我们之前发现，与骨形成相关的miR-9-5p在肌源性分化过程中随着时间的推移而增加。然而，miR-9-5p调节肌源性分化的机制在很大程度上仍然未知。在本研究中，我们首先检测了肌管形成和miR-9-5p，肌生成相关基因包括Dlx3， Myod1, Mef2c, Desmin， MyoG和Myf5在肌生成诱导下的表达。然后，我们在小鼠成肌前细胞系C2C12中，通过qPCR、western blot和成肌管诱导下，检测miR-9-5p或Dlx3过表达或敲低后的成肌转录因子的表达。通过荧光素酶测定，我们不仅证实了miR-9-5p与Dlx3之间的调控关系，还证实了Dlx3与其下游基因Myf5之间的调控关系，Myf5是肌源性分化的重要转录因子。结果表明，miR-9-5p通过增加肌源性转录因子表达和促进肌管形成来促进肌源性分化，而Dlx3则起到相反的作用。此外，荧光素酶检测显示，miR-9-5p与Dlx3的3'UTR结合，下调Dlx3的表达。Dlx3反过来通过结合Myf5启动子抑制Myf5的表达，最终抑制Myf5分化过程。总之，miR-9-5p/Dlx3/Myf5轴是调控肌源性分化的新途径，可能是治疗肌肉功能障碍相关疾病的潜在靶点。
MicroRNAs play an important role in myogenic differentiation, they bind to target genes and regulate muscle formation. We previously found that miR-9-5p, which is related to bone formation, was increased over time during the process of myogenic differentiation. However, the mechanism by which miR-9-5p regulates myogenic differentiation remains largely unknown. In the present study, we first examined myotube formation and miR-9-5p, myogenesis-related genes including Dlx3, Myod1, Mef2c, Desmin, MyoG and Myf5 expression under myogenic induction. Then, we detected the expression of myogenic transcription factors after overexpression or knockdown of miR-9-5p or Dlx3 in the mouse premyoblast cell line C2C12 by qPCR, western blot and myotube formation under myogenic induction. A luciferase assay was performed to confirm the regulatory relationships between not only miR-9-5p and Dlx3 but also Dlx3 and its downstream gene, Myf5, which is an essential transcription factor of myogenic differentiation. The results showed that miR-9-5p promoted myogenic differentiation by increasing myogenic transcription factor expression and promoting myotube formation, but Dlx3 exerted the opposite effect. Moreover, the luciferase assay showed that miR-9-5p bound to the 3’UTR of Dlx3 and downregulated Dlx3 expression. Dlx3 in turn suppressed Myf5 expression by binding to the Myf5 promoter, ultimately inhibiting the process of myogenic differentiation. In conclusion, the miR-9-5p/Dlx3/Myf5 axis is a novel pathway for the regulation of myogenic differentiation, and can be a potential target to treat the diseases related to muscle dysfunction.
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作者：
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DOI：
10.1073/pnas.0804438105
发表时间：
2008-09-16
影响因子：
11.1
作者：
Li, Zhaoyong;Hassan, Mohammad Q.;Stein, Gary S.
通讯作者：
Stein, Gary S.