MiR‐499 regulates myoblast proliferation and differentiation by targeting transforming growth factor β receptor 1

作者：Jiyao Wu, Binglin Yue, Xianyong Lan, Yanhuan Wang, Xingtang Fang, Yun Ma, Yueyu Bai, Xingshan Qi, Chunlei Zhang, Hong Chen · 发表于：Journal of Cellular Physiology · 年份：2018 · DOI：10.1002/jcp.26903 · 被引用次数：29 · 研究领域：MicroRNA in disease regulation、Muscle Physiology and Disorders、Circular RNAs in diseases

MicroRNAs (miRNAs or miRs) are small noncoding RNAs that play critical roles in muscle cell proliferation and differentiation via post-transcriptional regulation of gene expression. Here, based on our previous high-throughput sequencing results, we evaluated miRNA-499 (miR-499) functions during myoblast proliferation and differentiation. In addition, we analyzed miR-499 expression profiles and characterized the associated functional roles. MiR-499 is known to be a skeletal muscle fiber-type-associated miRNA. However, its roles in skeletal myoblast proliferation and differentiation are poorly understood. MiR-499 overexpression promoted C2C12 cell proliferation and significantly attenuated C2C12 cell myogenic differentiation. Furthermore, miR-499 inhibition enhanced C2C12 cell proliferation and suppressed C2C12 cell differentiation. Using dual-luciferase reporter assays and western blot analysis, we confirmed that miR-499 targeted transforming growth factor β receptor 1 (TGFβR1), a known regulator of skeletal myoblast development. Additionally, our RNA interference analysis, in which TGFβR1 was downregulated, showed that TGFβR1 significantly promoted the differentiation of C2C12 cells and inhibited their proliferation.