Elevated mir-145-5p is associated with skeletal muscle dysfunction and triggers apoptotic cell death in C2C12...

Skeletal muscle dysfunction is a common comorbidity of chronic obstructive pulmonary disease (COPD), and the molecular mechanisms regarding to the pathogenesis of this disease have not been elucidated. In this study, a novel miR-145-5p was significantly upregulated in the serum collected from patients with COPD-associated muscle atrophy, in contrast with the normal participants. Then, we evidenced that silencing of miR-145-5p suppressed cell death and elongated cell survival during cell culture process. Consistently, upregulation of miR-145-5p induced cell apoptosis and restrain cell viability in the C2C12 cells, suggesting that miR-145-5p contributes to cell death. Further experiments evidenced that miR-145-5p decreased the expression levels of phosphorylated PI3K (p-PI3K), Akt (p-Akt) and mTOR (p-mTOR) to inactivate the PI3K/Akt/mTOR pathway, and this pathway was also reactivated by miR-145-5p ablation. Finally, we proved that the protective effects of miR-145-5p ablation were abrogated by co-treating cells with PI3K inhibitor LY294002. Taken together, we concluded that miR-145-5p promoted cell death to facilitate muscle dysfunctions via inactivating the PI3K/Akt/mTOR pathway.