miR-9-5p promotes myogenic differentiation via the Dlx3/Myf5 axis

PeerJ

article

Liying Dong¹  Meng Wang¹  Xiaolei Gao⁴  Xuan Zheng⁴  Yixin Zhang⁴  Liangjie Sun⁴  Na Zhao⁵  Chong Ding¹  Zeyun Ma⁷  Yixiang Wang¹ 

[1] Central Laboratory, Peking University School and Hospital of Stomatology;National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology;Beijing Key Laboratory of Digital Stomatology, Peking University School and Hospital of Stomatology;Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology;Department of Restorative Dentistry and Biomaterials Sciences, Harvard School of Dental Medicine;Shanghai Stomatological Hospital, Fudan University;Department of VIP Service, Peking University School and Hospital of Stomatology

关键词: MiR-9-5p;    Dlx3;    Myf5;    Myogenic differentiation;   

DOI  :  10.7717/peerj.13360

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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.

【 授权许可】

CC BY