Inhibition of LncRNA MAAT Controls Multiple Types of Muscle Atrophy by Cis and Trans-regulatory Actions.

Muscle atrophy is associated with worse outcomes in a variety of diseases. Identification of a common therapeutic target would address a significant unmet clinical need. Here we identify a lncRNA (muscle atrophy associated transcript, lncMAAT) as a common regulator of skeletal muscle atrophy. LncMAAT is down-regulated in multiple types of muscle atrophy models both in vivo (denervation, AngII, fasting, immobilization, and aging induced muscle atrophy) and in vitro (AngII, H2O2 and TNFα induced muscle atrophy). Gain and loss of function analysis both in vitro and in vivo reveals that down-regulation 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.