Elevated mir-145-5p is associated with 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 patien...

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Bibliographic Details
Published in:Journal of muscle research and cell motility 2022-09, Vol.43 (3), p.135-145
Main Authors: Jin, Jing, Li, Fanyi, Fan, Caihong, Wu, Yu, He, Chunhui
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Ablation
AKT protein
Animal Anatomy
Apoptosis
Atrophy
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell culture
Cell death
Cell survival
Cell viability
Chronic obstructive pulmonary disease
Comorbidity
Histology
Life Sciences
Lung diseases
Molecular modelling
Morphology
Musculoskeletal system
Myotubes
Obstructive lung disease
Original Paper
Proteomics
Skeletal muscle
TOR protein
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Summary: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.
ISSN:0142-4319
1573-2657
DOI:10.1007/s10974-022-09624-2