Department of Obstetrics and Gynaecology, Chinese University of Hong Kong, Hong Kong, China.
PLoS One. 2012;7(3):e33766. doi: 10.1371/journal.pone.0033766. Epub 2012 Mar 16.
MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression in post-transcriptional fashion, and emerging studies support their importance in regulating many biological processes, including myogenic differentiation and muscle development. miR-29 is a promoting factor during myogenesis but its full spectrum of impact on muscle cells has yet to be explored. Here we describe an analysis of miR-29 affected transcriptome in C2C12 muscle cells using a high throughput RNA-sequencing platform. The results reveal that miR-29 not only functions to promote myogenic differentiation but also suppresses the transdifferentiation of myoblasts into myofibroblasts. miR-29 inhibits the fibrogenic differentiation through down-regulating both extracellular matrix genes and cell adhesion genes. We further demonstrate that miR-29 is under negative regulation by TGF-beta (TGF-β)-Smad3 signaling via dual mechanisms of both inhibiting MyoD binding and enhancing Yin Yang 1 (YY1)-recruited Polycomb association. Together, these results identify miR-29 as a pleiotropic molecule in both myogenic and fibrogenic differentiation of muscle cells.
微小 RNA（miRNAs）是一类非编码 RNA，通过转录后调控基因表达，越来越多的研究表明它们在调节许多生物学过程中发挥着重要作用，包括肌生成和肌肉发育。miR-29 是肌生成过程中的促进因子，但它对肌肉细胞的全面影响尚未被探索。在这里，我们使用高通量 RNA 测序平台描述了 miR-29 对 C2C12 肌肉细胞转录组的影响分析。结果表明，miR-29 不仅能促进肌生成，还能抑制成肌细胞向肌成纤维细胞的转分化。miR-29 通过下调细胞外基质基因和细胞黏附基因来抑制纤维生成分化。我们进一步证明，miR-29 受 TGF-β（TGF-β）-Smad3 信号的负调控，通过两种机制抑制 MyoD 结合并增强 YY1 募集的多梳蛋白相关。综上所述，这些结果表明 miR-29 是肌肉细胞在肌生成和纤维生成分化中具有多效性的分子。
