Abstract 16995: Inhibition of lncRNA MAAT Contributes to Multiple Types of Muscle Atrophy

Abstract

Background: Skeletal muscle atrophy is the consequence of many diseases, such as denervation, long-term inactivity, excessive fasting, ageing, and heart failure. Recently, increasing studies have shown that long noncoding RNAs (lncRNAs) play an important role in myogenesis and adult skeletal muscle regeneration. However, if lncRNAs are responsible for muscle atrophy remains largely unclear. Hypothesis: We aimed to select and investigate the role of lncRNAs in muscle atrophy. Methods and Results: LncRNA arrays indicated that several lncRNA transcripts were changed during denervation-induced muscle atrophy in mice. After detecting the expression of lncRNAs in multiple types of muscle atrophy in vivo (denervation, Angiotensin II and fasting induced muscle atrophy) and in vitro (Angiotensin II, H 2 O 2 and TNFα induced muscle atrophy) by qRT-PCRs, we identified that MAAT (Muscle Atrophy-Associated Transcript) was down-regulated in multiple types of muscle atrophy. Then lentivirus of shRNA and overexpression of MAAT were further used to study the role of MAAT in muscle atrophy in vitro and in vivo . We found that knockdown of MAAT promoted muscle atrophy, whereas upregulating MAAT prevented multiple types of muscle atrophy. Mechanistically, we found that MAAT negatively regulated the transcription of microRNA-29b through SOX6, and that MAAT influenced the expression of neighbor gene-MBNL by a cis-regulatory module. Conclusions: Inhibition of LncRNA MAAT contributes to muscle atrophy by increasing miR-29b and repressing MBNL. Overexpressing MAAT might be a novel approach to counteract muscle atrophy.