期刊
MOLECULAR THERAPY
卷 29, 期 3, 页码 1102-1119出版社
CELL PRESS
DOI: 10.1016/j.ymthe.2020.12.002
关键词
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资金
- Innovation Program of Shanghai Municipal Education Commission [2017-01-07-00-09-E00042]
- National Natural Science Foundation of China [81722008, 82020108002, 81911540486, 81900359, 81873774, 81701218]
- Science and Technology Commission of Shanghai Municipality [18410722200, 17010500100]
- Shanghai Sailing Program [19YF1416400]
- National Key Research and Development Project [2018YFE0113500]
- Chen Guang project - Shanghai Municipal Education Commission
- Shanghai Education Development Foundation [19CG45]
- Dawn program of the Shanghai Education Commission [19SG34]
lncMAAT is identified as a common regulator of skeletal muscle atrophy, which is downregulated in multiple models and can ameliorate muscle atrophy by negatively regulating miR29b and positively regulating Mbnl1 expression. Overexpression of lncMAAT may represent a promising therapy for muscle atrophy induced by different stimuli.
Muscle atrophy is associated with negative outcomes in a variety of diseases. Identification of a common therapeutic target would address a significant unmet clinical need. Here, we identify a long non-coding RNA (lncRNA) (muscle-atrophy-associated transcript, lncMAAT) as a common regulator of skeletal muscle atrophy. lncMAAT is downregulated in multiple types of muscle-atrophy models both in vivo (denervation, Angiotensin II [AngII], fasting, immobilization, and aging-induced muscle atrophy) and in vitro (AngII, H2O2, and tumor necrosis factor alpha [TNF-alpha]-induced muscle atrophy). Gain- and loss-of-function analysis both in vitro and in vivo reveals that downregulation of lncMAAT is sufficient to induce muscle atrophy, while overexpression of lncMAAT can ameliorate multiple types of muscle atrophy. Mechanistically, lncMAAT negatively regulates the transcription of miR29b through SOX6 by a trans-regulatory module and increases the expression of the neighboring gene Mbnl1 by a cis-regulatory module. Therefore, overexpression of lncMAAT may represent a promising therapy for muscle atrophy induced by different stimuli.
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