miR-208b modulating skeletal muscle development and energy homeostasis through targeting distinct targets

Embryonic and neonatal skeletal muscles grow via the proliferation and fusion of myogenic cells, whereas adult skeletal muscle adapts largely by remodeling pre-existing myofibers and optimizing metabolic balance. It has been reported that miRNAs played key roles during skeletal muscle development through targeting different genes at post-transcriptional level. In this study, we show that a single miRNA (miR-208b) can modulate both the myogenesis and homeostasis of skeletal muscle by distinct targets. As results, miR-208b accelerates the proliferation and inhibits the differentiation of myogenic cells by targeting the E-protein family member transcription factor 12 (TCF12). Also, miR-208b can stimulate fast-to-slow fiber conversion and oxidative metabolism program through targeting folliculin interacting protein 1 (FNIP1) but notTCF12 gene. Further, miR-208b could active the AMPK/PGC-1a signaling and mitochondrial biogenesis through targeting FNIP1. Thus, miR-208b could mediate skeletal muscle development and homeostasis through specifically targeting of TCF12 and FNIP1.

胚胎期与新生期的骨骼肌通过成肌细胞的增殖与融合实现生长，而成体骨骼肌的适应性重塑则主要依赖于对已存在肌纤维的改造及代谢平衡的优化。已有研究证实，微小RNA（miRNA）可通过转录后水平靶向不同基因，在骨骼肌发育过程中发挥关键调控作用。本研究表明，单一微小RNA（miR-208b）可通过作用于不同靶基因，同时调控骨骼肌的肌发生与稳态平衡。实验结果显示，miR-208b可通过靶向E蛋白家族成员转录因子12（TCF12），加速成肌细胞的增殖并抑制其分化。此外，miR-208b可通过靶向滤泡蛋白相互作用蛋白1（FNIP1）——而非TCF12基因——促进肌纤维快型向慢型转化，并激活氧化代谢程序。进一步研究发现，miR-208b可通过靶向FNIP1激活AMPK/PGC-1α信号通路与线粒体生物发生。综上，miR-208b可通过特异性靶向TCF12与FNIP1，介导骨骼肌的发育与稳态维持。