Circular RNA CircMYH8 regulates muscle proliferation, apoptosis and differentiation via binding miR-221 to activate p27

Many factors affect bovine skeletal muscle development, among which noncoding RNAs are very important. While circular RNAs (circRNAs) play a central role in various physiological and pathological processes, their potential role in muscle development is poorly understood. Here, we identified several differentially expressed circRNAs in fetal and adult skeletal muscle tissue sequencing data. They included a circRNA originating from exon 24 circularization of the myosin heavy chain protein 8 gene ( MYH8 ), circMYH8, which was significantly downregulated in the adult muscle tissue. We examined circMYH8's role in skeletal muscle cell proliferation, apoptosis, and differentiation through its overexpression or inhibition. Specifically, we used luciferase reporter gene assays, western blots, real-time reverse transcription quantitative PCR, cell counting kit 8, and 5-ethynyl-2-deoxyuridine to explore circMYH8's molecular sponge effect on bovine myoblast proliferation, apoptosis, and differentiation via competitively binding microRNA 221 to activate cyclin-dependent kinase inhibitor 1B. Then, we investigated circMYH8's role in promoting muscle regeneration by injecting a circMYH8 overexpression plasmid into muscle-injured mice. The results suggest that circMYH8 inhibits bovine myoblast proliferation and facilitates cell apoptosis and differentiation acts through the miR-221/P27 axis. This study shows that circMYH8 is a potential myogenesis-related factor and provides new evidence for elucidating complex molecular mechanisms and a better understanding of the function of mammalian circular RNAs in muscle development.