MiR‐222‐3p suppresses C2C12 myoblast proliferation and differentiation via the inhibition of IRS‐1/PI3K/Akt pathway

Abstract Numerous studies have revealed the profound impact of microRNAs on regulating skeletal muscle development and regeneration. However, the biological function and regulation mechanism of miR‐222‐3p in skeletal muscle remains largely unknown. In this study, miR‐222‐3p was found to be abundantly expressed in the impaired skeletal muscles, indicating that it might have function in the development and regeneration process of the skeletal muscle. MiR‐222‐3p overexpression impeded C2C12 myoblast proliferation and myogenic differentiation, whereas inhibition of miR‐222‐3p got the opposite results. The dual‐luciferase reporter assay showed that insulin receptor substrate‐1 (IRS‐1) was the target gene of miR‐222‐3p. We next found that knockdown of IRS‐1 could obviously suppress C2C12 myoblast proliferation and differentiation. Additionally, miR‐222‐3p‐induced repression of myoblast proliferation and differentiation was verified to be associated with a decrease in phosphoinositide 3‐kinase (PI3K)‐Akt signaling. Overall, we demonstrated that miR‐222‐3p inhibited C2C12 cells myogenesis via IRS‐1/PI3K/Akt pathway. Therefore, miR‐222‐3p may be used as a therapeutic target for alleviating muscle loss caused by inherited and nonhereditary diseases.