Elevated miR-145-5p is Associated with Chronic Obstructive Pulmonary Disease (COPD) Associated Skeletal Muscle Dysfunction and Triggers Apoptotic Cell Death in C2C12 Myotubes

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, the primary myotubes was isolated and cultured in vitro , and 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 myotube 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 in the C2C12 cells, and this pathway was also reactivated by miR-145-5p ablation in the primary myotube cells. Finally, we proved that the protective effects of miR-145-5p ablation on the primary myotube cells were abrogated by co-treating cells with PI3K inhibitor LY294002. Taken together, we concluded that miR-145-5p promoted myotube cell death to facilitate COPD-associated muscle dysfunctions via inactivating the PI3K/Akt/mTOR pathway.