Comprehensive analysis of miRNA expression, secretion profile, and functional network during myogenesis in response to spaceflight.

MicroRNAs (miRNAs) are key regulators of skeletal muscle development and homeostasis. As secretory factors, previous studies have identified and validated a space flight-associated circulating microRNA (miRNA) signature in response to space flight. However, the muscle-derived miRNAs are not clear. Here, we comprehensively analyzed the variations of miRNA during mouse myoblast myogenesis in response to space flight, including expression and secretion. We validated some miRNA expression by qRT-PCR analysis in the limb muscle of a disuse-induced atrophy mouse model, mimicking the unloading following microgravity. Functional assays using miRNA mimics further supported the regulatory roles of some miRNAs in target gene expression, as well as in myoblast proliferation and differentiation. These results suggest that deregulation of these miRNAs may play a functional role in muscle atrophy, and they could be candidate biomarkers of muscle atrophy-associated muscular disease. Importantly, our analysis also suggests that spaceflight may regulate miRNA secretion and retention by modulating RNA-binding proteins (RBPs). Secreted miRNAs originating from skeletal muscle cells have been implicated in various diseases affecting the nervous and skeletal systems. Collectively, these findings highlight the potential role of skeletal muscle-derived miRNAs in systemic adaptation to spaceflight.