Involvement of microRNA-133a-3p with the conversion of muscle fiber type in human skeletal myogenesis.

Abstract

Objective: Skeletal muscle fiber conversion bears a part in multiple myopathies, and one of those is Sarcopenia which is known to correlate with aging, nutritional deficiency, and so on. In this study, we focused on muscle specific enriched microRNAs (myomirs) to understand the mechanisms of muscle fiber conversion.Method & Results: In-silico study, we selected the microRNA-133a-3p (miR-133a), a myomir relevant to the skeletal myogenesis. Using the human iPS cell-derived skeletal myogenesis system, we identified that expression level of miR -133a was elevated with a peak at day 5 after the induction of myogenesis. Overexpression of miR-133a mimic or inhibitor at the beginning of myogenesis increased mRNA expression of Myh7, a specific marker of slow oxidative myotube, or Myh1, a marker of fast-type myotube, respectively. Furthermore, we found that, under the serumdeprived culture condition, overexpression of miR-133a mimic preserved the cell feature of oxidative fibers, although miR-133a inhibition deformed the tubular formation of oxidative myotubes. Conclusion: MicroRNA-133a functioned to buttress the gene expression of oxidative fiber-specified myosin heavy chain, and to preserve myotubes from nutritional stress, suggesting the possibility that miR-133a would be a therapeutic target for sarcopenia.