Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 76, Issue 24, Pages 5041-5054Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-019-03165-7
Keywords
microRNA; miR-17-92; Skeletal myogenesis; Myogenic differentiation; Muscle regeneration
Categories
Funding
- National Natural Science Foundation of China [31472159, 31272520]
- Fundamental Research Funds for the Central Universities of China [2572016EAJ3]
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Skeletal myogenesis is a highly coordinated process that involves cell proliferation, differentiation and fusion controlled by a complex gene regulatory network. The microRNA gene cluster miR-17-92 has been shown to be related to this process; however, the exact role of each cluster member remains unclear. Here, we show that miR-17 and miR-20a could effectively promote the differentiation of both C2C12 myoblasts and primary bovine satellite cells. In contrast, miR-18a might play a negative role in C2C12 cell differentiation, while miR-19 and miR-92a had little influence. Transcriptome and target analyses revealed that miR-17 could act on Ccnd2, Jak1 and Rhoc genes that are critical for cell proliferation and/or fusion. Notably, the addition of miR-19 could reverse the lethal effect of miR-17 and could thus facilitate the maturation of myotubes. Furthermore, by co-injecting the lentiviral shRNAs of miR-17 and miR-19 into mouse tibialis anterior muscles, we demonstrated the wound healing abilities of the two miRNAs. Our findings indicate that in combination with miR-19, miR-17 is a potent inducer of skeletal muscle differentiation.
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