Zhang Yidi, Wang Teng, Wang Ziang, Shi Xin'e, Jin Jianjun
Laboratory of Animal Fat Deposition and Muscle Development, Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, China.
J Cachexia Sarcopenia Muscle. 2025 Apr;16(2):e13747. doi: 10.1002/jcsm.13747.
Skeletal muscle is the most abundant tissue in the human body and is responsible for movement, metabolism, energy production and longevity. Muscle atrophy is a frequent complication of several diseases and occurs when protein degradation exceeds protein synthesis. Genetics, ageing, nerve injury, weightlessness, cancer, chronic diseases, the accumulation of metabolic byproducts and other stimuli can lead to muscle atrophy. Muscular dystrophy is a neuromuscular disorder, part of which is caused by the deficiency of dystrophin protein and is mostly related to genetics. Muscle atrophy and muscular dystrophy are accompanied by dynamic changes in transcriptomic, translational and epigenetic regulation. Multiple signalling pathways, such as the transforming growth factor-β (TGF-β) signalling pathway, the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway, inflammatory signalling pathways, neuromechanical signalling pathways, endoplasmic reticulum stress and glucocorticoids signalling pathways, regulate muscle atrophy. A large number of long noncoding RNAs (lncRNAs) have been found to be abnormally expressed in atrophic muscles and dystrophic muscles and regulate the balance of muscle protein synthesis and degradation or dystrophin protein expression. These lncRNAs may serve as potential targets for treating muscle atrophy and muscular dystrophy. In this review, we summarized the known lncRNAs related to muscular dystrophy and muscle atrophy induced by denervation, ageing, weightlessness, cachexia and abnormal myogenesis, along with their molecular mechanisms. Finally, we explored the potential of using these lncRNAs as therapeutic targets for muscle atrophy and muscular dystrophy, including the methods of discovery and clinical application prospects for functional lncRNAs.
骨骼肌是人体中最丰富的组织，负责运动、新陈代谢、能量产生和寿命。肌肉萎缩是多种疾病常见的并发症，当蛋白质降解超过蛋白质合成时就会发生。遗传、衰老、神经损伤、失重、癌症、慢性疾病、代谢副产物的积累和其他刺激都可能导致肌肉萎缩。肌肉营养不良是一种神经肌肉疾病，部分原因是肌营养不良蛋白缺乏，且大多与遗传有关。肌肉萎缩和肌肉营养不良伴随着转录组、翻译和表观遗传调控的动态变化。多种信号通路，如转化生长因子-β（TGF-β）信号通路、磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）/雷帕霉素靶蛋白（mTOR）通路、炎症信号通路、神经机械信号通路、内质网应激和糖皮质激素信号通路，调节肌肉萎缩。大量长链非编码RNA（lncRNA）已被发现在萎缩性肌肉和营养不良性肌肉中异常表达，并调节肌肉蛋白质合成与降解的平衡或肌营养不良蛋白的表达。这些lncRNA可能成为治疗肌肉萎缩和肌肉营养不良的潜在靶点。在本综述中，我们总结了已知的与肌肉营养不良以及由去神经支配、衰老、失重、恶病质和异常肌生成诱导的肌肉萎缩相关的lncRNA，以及它们的分子机制。最后，我们探讨了将这些lncRNA用作肌肉萎缩和肌肉营养不良治疗靶点的潜力，包括功能性lncRNA的发现方法和临床应用前景。
