Li Rongyang, Li Bojiang, Cao Yan, Li Weijian, Dai Weilong, Zhang Liangliang, Zhang Xuan, Ning Caibo, Li Hongqiang, Yao Yilong, Tao Jingli, Jia Chao, Wu Wangjun, Liu Honglin
Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China.
Mol Ther Nucleic Acids. 2021 Feb 26;24:200-211. doi: 10.1016/j.omtn.2021.02.025. eCollection 2021 Jun 4.
Emerging studies have indicated that long non-coding RNAs (lncRNAs) play important roles in skeletal muscle growth and development. Nevertheless, it remains challenging to understand the function and regulatory mechanisms of these lncRNAs in muscle biology and associated diseases. Here, we identify a novel lncRNA, , that is significantly upregulated during myoblast differentiation and is highly expressed in skeletal muscle. We validated that promotes myoblast differentiation . Mechanistically, gives rise to mature microRNA (miR)-22-3p, which inhibits its target gene, histone deacetylase 4 (), thereby increasing the downstream myocyte enhancer factor 2C () and ultimately promoting myoblast differentiation. Furthermore, , we documented that knockdown delays repair and regeneration following skeletal muscle injury and further causes a significant decrease in weight following repair of an injured muscle. Additionally, gives rise to miR-22-3p to restrict expression, thereby promoting the differentiation and regeneration of skeletal muscle. Given the conservation of between mice and humans, might constitute a promising new therapeutic target for skeletal muscle injury, skeletal muscle atrophy, as well as other skeletal muscle diseases.
新兴研究表明,长链非编码RNA(lncRNAs)在骨骼肌生长发育中发挥重要作用。然而,了解这些lncRNAs在肌肉生物学及相关疾病中的功能和调控机制仍然具有挑战性。在此,我们鉴定出一种新型lncRNA,其在成肌细胞分化过程中显著上调且在骨骼肌中高表达。我们验证了该lncRNA促进成肌细胞分化。机制上,该lncRNA产生成熟的微小RNA(miR)-22-3p,后者抑制其靶基因组蛋白去乙酰化酶4(HDAC4),从而增加下游的肌细胞增强因子2C(MEF2C)并最终促进成肌细胞分化。此外,我们证明敲低该lncRNA会延迟骨骼肌损伤后的修复和再生,并进一步导致受伤肌肉修复后体重显著下降。另外,该lncRNA产生miR-22-3p以限制HDAC4表达,从而促进骨骼肌的分化和再生。鉴于该lncRNA在小鼠和人类之间具有保守性,它可能成为治疗骨骼肌损伤、骨骼肌萎缩以及其他骨骼肌疾病的一个有前景的新治疗靶点。