Biotherapy Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
Laboratory Medicine, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
Cells. 2022 Nov 4;11(21):3497. doi: 10.3390/cells11213497.
Long non-coding RNAs (lncRNAs) regulate a series of physiological processes and play an important role in development, metabolism and disease. Our previous studies showed that lncRNAs involved in skeletal muscle differentiation. Here, we demonstrated that lncRNA Has2os is highly expressed in skeletal muscle and significantly elevated during skeletal cell differentiation. The knockdown of Has2os inhibited myocyte fusion and impeded the expression of the myogenic factors MyHC and Mef2C. Mechanically, Has2os regulates skeletal muscle differentiation by inhibiting the JNK/MAPK signaling pathway. Furthermore, we also revealed that Has2os is involved in the early stage of regeneration after muscle injury, and the JNK/MAPK signaling pathway is activated at both protein and mRNA levels during early repair. Our results demonstrate the new function of lncRNA Has2os, which plays crucial roles during skeletal muscle differentiation and muscle regeneration, providing a basis for the therapy of lncRNA-related muscle diseases.
长链非编码 RNA(lncRNA)调节一系列生理过程,在发育、代谢和疾病中发挥重要作用。我们之前的研究表明,lncRNA 参与了骨骼肌分化。在这里,我们证明 lncRNA Has2os 在骨骼肌中高度表达,并在骨骼肌细胞分化过程中显著上调。Has2os 的敲低抑制肌细胞融合,并阻碍肌球蛋白重链(MyHC)和 MEF2C 等肌生成因子的表达。在机制上,Has2os 通过抑制 JNK/MAPK 信号通路来调节骨骼肌分化。此外,我们还揭示了 Has2os 参与肌肉损伤后的早期再生过程,在早期修复过程中,JNK/MAPK 信号通路在蛋白质和 mRNA 水平上均被激活。我们的研究结果表明,lncRNA Has2os 具有新的功能,在骨骼肌分化和肌肉再生过程中发挥关键作用,为 lncRNA 相关肌肉疾病的治疗提供了依据。