Jia Long, Li Yue-Feng, Wu Guo-Fang, Song Zi-Yi, Lu Hong-Zhao, Song Cheng-Chuang, Zhang Qiang-Ling, Zhu Jia-Yu, Yang Gong-She, Shi Xin-E
Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
Int J Mol Sci. 2013 Dec 27;15(1):296-308. doi: 10.3390/ijms15010296.
MicroRNAs constitute a class of ~22-nucleotide non-coding RNAs. They modulate gene expression by associating with the 3' untranslated regions (3' UTRs) of messenger RNAs (mRNAs). Although multiple miRNAs are known to be regulated during myoblast differentiation, their individual roles in muscle development are still not fully understood. In this study, we showed that miR-199a-3p was highly expressed in skeletal muscle and was induced during C2C12 myoblasts differentiation. We also identified and confirmed several genes of the IGF-1/AKT/mTOR signal pathway, including IGF-1, mTOR, and RPS6KA6, as important cellular targets of miR-199a-3p in myoblasts. Overexpression of miR-199a-3p partially blocked C2C12 myoblast differentiation and the activation of AKT/mTOR signal pathway, while interference of miR-199a-3p by antisense oligonucleotides promoted C2C12 differentiation and myotube hypertrophy. Thus, our studies have established miR-199a-3p as a potential regulator of myogenesis through the suppression of IGF-1/AKT/mTOR signal pathway.
微小RNA构成了一类约22个核苷酸的非编码RNA。它们通过与信使RNA（mRNA）的3'非翻译区（3'UTR）结合来调节基因表达。尽管已知多个微小RNA在成肌细胞分化过程中受到调控，但其在肌肉发育中的个体作用仍未完全明确。在本研究中，我们发现miR-199a-3p在骨骼肌中高表达，并在C2C12成肌细胞分化过程中被诱导。我们还鉴定并证实了IGF-1/AKT/mTOR信号通路的几个基因，包括IGF-1、mTOR和RPS6KA6，是成肌细胞中miR-199a-3p的重要细胞靶点。miR-199a-3p的过表达部分阻断了C2C12成肌细胞的分化以及AKT/mTOR信号通路的激活，而反义寡核苷酸对miR-199a-3p的干扰则促进了C2C12的分化和肌管肥大。因此，我们的研究通过抑制IGF-1/AKT/mTOR信号通路，将miR-199a-3p确立为肌生成的潜在调节因子。
