Long Noncoding RNA lncMUMA Reverses Established Skeletal Muscle Atrophy following Mechanical Unloading

Zong Kang Zhang, Jie Li, Daogang GUAN, Chao LIANG, Zhenjian Zhuo, Jin LIU, Aiping LYU, Ge ZHANG, Bao Ting Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Reversing established muscle atrophy following mechanical unloading is of great clinical challenge. Long noncoding RNAs (lncRNAs) have been demonstrated to play important roles in myogenesis. Here we identified a lncRNA (mechanical unloading-induced muscle atrophy-related lncRNA [lncMUMA]) enriched in muscle, which was the most downregulated lncRNA during muscle atrophy development in hindlimb suspension (HLS) mice. The in vitro and in vivo data demonstrated that the decreased expression levels of lncMUMA closely associated with a reduction of myogenesis during mechanical unloading. Mechanistically, lncMUMA promoted myogenic differentiation by functioning as a miR-762 sponge to regulate the core myogenic regulator MyoD in vitro. The enforced expression of lncMUMA relieved the decreases in MyoD protein and muscle mass in miR-762 knockin mice. Therapeutically, the enforced expression of lncMUMA improved the in vitro myogenic differentiation of myoblasts under microgravity simulation, prevented the muscle atrophy development, and reversed the established muscle atrophy in HLS mice. These findings identify lncMUMA as an anabolic regulator to reverse established muscle atrophy following mechanical unloading. Reversing established muscle atrophy following mechanical unloading is of great clinical challenge. Zhang et al. identify lncRNA lncMUMA acts as a miR-762 sponge to regulate MyoD protein, resulting in promoting muscle differentiation. lncMUMA could be a novel anabolic therapeutic agent to reverse established skeletal muscle atrophy following mechanical unloading.

Original languageEnglish
Pages (from-to)2669-2680
Number of pages12
JournalMolecular Therapy
Volume26
Issue number11
DOIs
Publication statusPublished - 7 Nov 2018

Scopus Subject Areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

User-Defined Keywords

  • long noncoding RNA
  • mechanical unloading
  • skeletal muscle atrophy

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