Institute of Cellular and Molecular Biology, School of Life Science, Jiangsu Normal University, Xuzhou, China.
FASEB J. 2021 Feb;35(2):e21324. doi: 10.1096/fj.202001992R.
The noncoding RNAs play important role in growth and development of mammalian skeletal muscle. Recent work has shown that circRNAs are abundant in skeletal muscle tissue, with significant changes in their expression patterns during muscle development and aging. We identified a novel circRNA called circARID1A that is highly expressed in mice skeletal muscle compare to its linear transcript. Experiments shown that circARID1A significantly inhibited the process of C2C12 cell proliferation and promoted its differentiation. Interactions between circRNA and miRNA were screened by miRNA gene chip sequencing. The results indicated that circARID1A can sponge miR-6368, which was further verified by miRNA sensor and other experiments. Besides, miR-6368 is a commonly expressed miRNA that regulates the expression of several target genes including Tlr4. A mouse model of skeletal muscle injury was successfully established to explore the role of circARID1A in skeletal muscle development and regeneration in vivo. Moreover, we found the overexpression of circARID1A significantly promoted the regeneration of skeletal muscle. The results of our study suggest that circARID1A may regulate skeletal muscle cell development and regeneration by sponging miR-6368.
非编码 RNA 在哺乳动物骨骼肌的生长和发育中发挥重要作用。最近的研究表明,circRNAs 在骨骼肌组织中大量存在,其表达模式在肌肉发育和衰老过程中发生显著变化。我们鉴定了一种称为 circARID1A 的新型 circRNA,它在小鼠骨骼肌中的表达水平明显高于其线性转录本。实验表明,circARID1A 显著抑制 C2C12 细胞的增殖过程,并促进其分化。通过 miRNA 基因芯片测序筛选 circRNA 与 miRNA 之间的相互作用。结果表明,circARID1A 可以海绵吸附 miR-6368,这通过 miRNA 传感器和其他实验进一步得到验证。此外,miR-6368 是一种表达广泛的 miRNA,可调节包括 Tlr4 在内的几个靶基因的表达。成功建立了骨骼肌损伤的小鼠模型,以探索 circARID1A 在体内骨骼肌发育和再生中的作用。此外,我们发现 circARID1A 的过表达显著促进了骨骼肌的再生。我们的研究结果表明,circARID1A 可能通过海绵吸附 miR-6368 来调节骨骼肌细胞的发育和再生。