Inhibition of lncRNA MAAT Controls Multiple Types of Muscle Atrophy by cis- and trans-Regulatory Actions.
Mol Ther
; 29(3): 1102-1119, 2021 03 03.
Article
em En
| MEDLINE
| ID: mdl-33279721
ABSTRACT
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-α]-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 miR-29b 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Atrofia Muscular
/
Sequências Reguladoras de Ácido Nucleico
/
MicroRNAs
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Fatores de Transcrição SOXD
/
RNA Longo não Codificante
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Ther
Assunto da revista:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China