MicroRNAs Play Mega Role in Regulation of Muscle Size

Decreased skeletal muscle size, aka muscle atrophy, occurs during a variety of conditions including disuse, diabetes, aging, HIV/AIDS, and cancer resulting in decreased quality of life and increased morbidity and mortality risk. Numerous studies have shown that activation of protein degradation pathways in muscle plays a central role in the development of muscle atrophy. Further, recent research demonstrates that microRNAs (miRs) regulate an array of signaling pathways in different tissues, including protein degradation pathways in muscle. PURPOSE: Therefore, the purpose of these experiments was investigate the role and regulation of two microRNAs, miR-23a and miR-182, proposed to play a role in protein degradation pathways in muscle. METHODS: MiR-23a and miR-182 levels were measured via qPCR in both in vivo and in vitro models of muscle atrophy. MiR overexpression experiments followed by qPCR and western blotting analysis were performed to verify specific targeting. RESULTS: Both miR-23a and miR-182 are significantly decreased in muscle of diabetic rats and in vitro in C2C12 muscle cells treated with glucocorticoids. This decrease is due to, at least in part, miR-23a and miR-182 being packaged into exosomes and removed from the muscle cells. Additionally, miR-182 was found directly target and suppress FoxO3 in muscle, and prevent FoxO3 mediated atrophy signaling in vitro. CONCLUSION: Both miR-23a and miR-182 play a significant role in the regulation of muscle atrophy signaling. Source of funding: NIH T32 DK007656 (M.B.H.), and NIH R01DK95610 and VA Merit (S.R.P.)