College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Shanxi, P.R. China.
Department of Nephrology, Shanghai General Hosptial, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
J Cell Biochem. 2023 Sep;124(9):1379-1390. doi: 10.1002/jcb.30453. Epub 2023 Aug 10.
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.
大量研究揭示了 microRNAs 对调节骨骼肌发育和再生的深远影响。然而，miR-222-3p 在骨骼肌中的生物学功能和调控机制在很大程度上仍然未知。本研究发现 miR-222-3p 在受损骨骼肌中大量表达，表明其可能在骨骼肌的发育和再生过程中发挥作用。miR-222-3p 的过表达抑制了 C2C12 成肌细胞的增殖和肌生成分化，而抑制 miR-222-3p 则得到了相反的结果。双荧光素酶报告基因检测表明胰岛素受体底物-1（IRS-1）是 miR-222-3p 的靶基因。我们随后发现，敲低 IRS-1 可以明显抑制 C2C12 成肌细胞的增殖和分化。此外，miR-222-3p 诱导的成肌细胞增殖和分化抑制被证实与磷酸肌醇 3-激酶（PI3K）-Akt 信号通路的减少有关。综上所述，我们证明了 miR-222-3p 通过 IRS-1/PI3K/Akt 通路抑制 C2C12 细胞的肌生成。因此，miR-222-3p 可能被用作减轻遗传性和非遗传性疾病引起的肌肉损失的治疗靶点。
