miR-122-5p negatively regulates the transforming growth factor-β/Smad signaling pathway in skeletal muscle myogenesis

Regeneration remains a major challenge in skeletal muscle repair after injury. Recently, transforming growth factor-beta (TGF-beta)/Smad pathway was found to play an important role in inhibiting myogenesis, a crucial stage in skeletal muscle regeneration. In our previous study, microRNA-122-5p (miR-122) was proved to have the function of downregulating TGF-beta/Smad pathway. Theoretically, miR-122 might also be involved in the process of skeletal muscle myogenesis through the regulation of TGF-beta/Smad pathway. In this study, we aimed to investigate the impact of miR-122 on skeletal muscle myogenesis and explore its underlying mechanism. Results showed that miR-122 and myogenic markers were downregulated in C2C12 cells after TGF-beta stimulation, and miR-122 overexpression could restore the myogenesis inhibited by TGF-beta. We then located TGFBR2 as the direct target of miR-122 and discovered the effect of miR-122 overexpression could be rescued by TGFBR2 overexpression. Further, the downstream molecules of TGFBR2 in the TGF-beta/Smad pathway were found to be suppressed by miR-122. In conclusion, miR-122 could suppress the TGF-beta/Smad signalling pathway by directly targeting TGFBR2 and, consequently, restore myogenesis. Significance of the study Regeneration remains a major challenge in skeletal muscle repair after injury. In this study, it was found that miR-122 could suppress the TGF-beta/Smad signalling pathway by directly targeting TGFBR2 and, consequently, restore myogenesis. Our findings could inspire future experiments on the role of miRs in skeletal muscle diseases and future translational studies on potential novel gene therapy for skeletal muscle injury.