MicroRNA in myogenesis and muscle atrophy

Abstract

Purpose of review: To understand the impact of microRNA on myogenesis and muscle wasting in order to provide valuable information for clinical investigation.

Recent findings: Muscle wasting increases the risk of morbidity/mortality in primary muscle diseases, secondary muscle disorders and elderly population. Muscle mass is controlled by several different signalling pathways. Insulin-like growth factor/PI3K/Akt is a positive signalling pathway, as it increases muscle mass by increasing protein synthesis and decreasing protein degradation. This pathway is directly and/or indirectly downregulated by miR-1, miR-133, miR-206 or miR-125b, and upregulated by miR-23a or miR-486. Myostatin and the transforming growth factor-β signalling pathway are negative regulators that cause muscle wasting. An increase of miR-27 reduces myostatin and increases muscle cell proliferation. Muscle regeneration capacity also plays a significant role in the regulation of muscle mass. This review comprehensively describes the effect of microRNA on myoblasts proliferation and differentiation, and summarizes the varied influences of microRNA on different muscle atrophy.

Summary: Growing evidence indicates that microRNAs significantly impact muscle growth, regeneration and metabolism. MicroRNAs have a great potential to become diagnostic and/or prognostic markers, therapeutic agents and therapeutic targets.

FIGURE 1

MicroRNA regulation of IGF/PI3K/Akt signalling: Muscle-specific miR-1 regulates IGF/PI3K/Akt signalling by directly targeting IGF-1. The activated state of the IGF-1 reciprocally regulates miR-1 expression through the FoxO transcription factor. FoxO binds on miR-1 promoter region and increases transcription of miR-1. miR-206 and miR-133 also target IGF-1. miR-133 has a conserved and functional binding site in the 3′-UTR of IGF-1R, which results in decreased IGF-1R abundance. miR-125b targets IGF-2. miR-486 and miR-17-92 downregulate PTEN, thus increasing pAkt which, in turn, phosphorylates FoxO resulting in its inactivation. Inactivation of FoxO limits muscle wasting. miR-23a suppresses the translation of both atrogin-1 and MuRF1 in a 3′-UTR-dependent manner, thus directly inhibiting muscle atrophy.