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Regulation of muscle atrophy by microRNAs: 'AtromiRs' as potential target in cachexia
Wouter R P H van de Worp1, Jan Theys2, Ardy van Helvoort1,3
1Department of Respiratory Medicine, NUTRIM.
Purpose Of Review:
To provide an overview and describe the mode of action of miRNAs recently implicated in muscle atrophy, and discuss the challenges to explore their potential as putative therapeutic targets in cachexia.
Recent Findings:
Recent work showed differentially expressed miRNAs in skeletal muscle of patients with cachexia-associated diseases. Studies using experimental models revealed miRNA regulation of the anabolic IGF-1 and catabolic TGF- β/myostatin pathways, and downstream protein synthesis and proteolysis signaling in control of muscle mass.
Summary:
Cachexia is a complex metabolic condition associated with progressive body weight loss, wasting of skeletal muscle mass and decrease in muscle strength. MiRNAs play a central role in post-transcriptional gene regulation by targeting mRNAs, thereby coordinating and fine-tuning many cellular processes. MiRNA expression profiling studies of muscle biopsies have revealed differentially expressed miRNAs in patients with low muscle mass or cachexia. Evaluation in experimental models has revealed muscle atrophy, inhibition of protein synthesis and activation of proteolysis in response to modulation of specific miRNAs, termed 'atromiRs' in this review. These exciting findings call for further studies aimed at exploring the conservation of differentially expressed miRNAs across diseases accompanied by cachexia, identification of miRNA clusters and targets involved in muscle atrophy, and probing whether these miRNAs might be potential therapeutic targets for cachexia.
Insights
MicroRNAs (miRNAs) are key regulators of muscle mass. Dysregulated miRNAs, or "atromiRs," contribute to muscle atrophy in cachexia, presenting potential therapeutic targets.
Area of Science:
- Molecular Biology
- Genetics
- Physiology
Background:
- Cachexia involves progressive muscle wasting and strength loss.
- MicroRNAs (miRNAs) are crucial post-transcriptional regulators of gene expression.
- Altered miRNA expression is observed in skeletal muscle of cachexia patients.
Purpose of the Study:
- To review the role of miRNAs in muscle atrophy.
- To describe the mechanism of action of miRNAs in cachexia.
- To discuss the therapeutic potential of targeting miRNAs in cachexia.
Main Methods:
- Review of recent literature on miRNAs and muscle atrophy.
- Analysis of miRNA expression profiling studies in cachexia.
- Examination of experimental models of muscle wasting.
Main Results:
- Differential miRNA expression is found in skeletal muscle associated with cachexia.
- miRNAs regulate key anabolic (IGF-1) and catabolic (TGF-β/myostatin) pathways.
- Modulation of specific miRNAs (atromiRs) impacts protein synthesis and proteolysis.
Conclusions:
- miRNAs, particularly 'atromiRs,' are implicated in the pathogenesis of muscle atrophy in cachexia.
- Further research is needed to identify conserved miRNAs and their targets.
- miRNAs represent promising therapeutic targets for cachexia treatment.