Skeletal muscle differentiation is a highly coordinated process that involves many cellular signaling pathways and microRNAs (miRNAs). A group of muscle-specific miRNAs has been reported to promote myogenesis by suppressing key signaling pathways for cell growth. However, the functional role and regulatory mechanism of most non-muscle-specific miRNAs with stage-specific changes during differentiation are largely unclear. Here, we describe the functional characterization of miR-101a/b, a pair of non-muscle-specific miRNAs that show the largest change among a group of transiently upregulated miRNAs during myogenesis in C2C12 cells. The overexpression of miR-101a/b inhibits myoblast differentiation by suppressing the p38/MAPK, Interferon Gamma, and Wnt pathways and enhancing the C/EBP pathway. Mef2a, a key protein in the p38/MAPK pathway, was identified as a direct target of miR-101a/b. Interestingly, we found that the long non-coding RNA (lncRNA) Malat1, which promotes muscle differentiation, interacts with miR-101a/b, and this interaction competes with Mef2a mRNA to relieve the inhibition of the p38/MAPK pathway during myogenesis. These results uncovered a “braking” role in differentiation of transiently upregulated miRNAs and provided new insights into the competing endogenous RNA (ceRNA) regulatory mechanism in myoblast differentiation and myogenesis.
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The authors thank Qiao-Juan Huang and Xiao-Hong Chen for their technical assistance. This work was supported by the National Natural Science Foundation of China (31970604, 31701116, 31770879, 31771459, 31900903, 81870449, 81974436), the Major Research Plan of the National Natural Science Foundation of China (91940000), the Fundamental Research Funds for the Central Universities (20lgpy112), and Science and Technology New Star in ZhuJiang Guangzhou City (201806010151).
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Liu, S., Xie, S., Chen, H. et al. The functional analysis of transiently upregulated miR-101 suggests a “braking” regulatory mechanism during myogenesis. Sci. China Life Sci. (2021). https://doi.org/10.1007/s11427-020-1856-5
- p38/MAPK signaling pathway
- skeletal muscle differentiation