Functions and Therapeutic Potentials of Long Noncoding RNA in Skeletal Muscle Atrophy and Dystrophy

Abstract

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.