Muscle-enriched microRNA-486-mediated regulation of muscular atrophy and exercise

The objectives of this review were to understand the impact of microRNA-486 on myogenesis and muscle atrophy, and the change of microRNA-486 following exercise, and provide valuable information for improving muscle atrophy based on exercise intervention targeting microRNA-486. Muscle-enriched microRNAs (miRNAs), also referred to as myomiRs, control various processes in skeletal muscles, from myogenesis and muscle homeostasis to different responses to environmental stimuli such as exercise. MicroRNA-486 is a miRNA in which a stem-loop sequence is embedded within the ANKYRIN1 (ANK1) locus and is strictly conserved across mammals. MicroRNA-486 is involved in the development of muscle atrophy caused by aging, immobility, prolonged exposure to microgravity, or muscular and neuromuscular disorders. PI3K/AKT signaling is a positive pathway, as it increases muscle mass by increasing protein synthesis and decreasing protein degradation. MicroRNA-486 can activate this pathway by inhibiting phosphatase and tensin homolog (PTEN), it may also indirectly inhibit the HIPPO signaling pathway to promote cell growth. Exercises regulate microRNA-486 expression both in blood and muscle. This review focused on the recent elucidation of sarcopenia regulation by microRNA-486 and its effects on pathological states, including primary muscular disease, secondary muscular disorders, and age-related sarcopenia. Additionally, the role of exercise in regulating skeletal muscle-enriched microRNA-486 was highlighted, along with its physiological significance. Growing evidence indicates that microRNA-486 significantly impacts the development of muscle atrophy. MicroRNA-486 has great potential to become a therapeutic target for improving muscle atrophy through exercise intervention.