Regulation of muscle atrophy by microRNAs

Abstract

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.

Liquid Biopsy for Cancer Cachexia: Focus on Muscle-Derived microRNAs

“…Other skeletal muscle-derived miRNAs have been more recently found to be modulated in cancer cachexia, also having in most cases an important prognostic value [131,168,169].…”

“…More recently, other skeletal muscle miRNAs (miR18a, miR208a, miR208b, miR422a, miR499, miR542-5p and miR542-3p) have been proposed to play a role in the pathophysiology of cancer cachexia [131,168]. In particular, both in vitro and in vivo studies (human samples but also mouse models) showed overexpression of miR18a, miR422a; miR542-5p/3p in skeletal muscle tissue during muscle wasting conditions [168].…”

Non-coding RNAs in exosomes and adipocytes cause fat loss during cancer cachexia

“…Disordered ncRNAs can affect the ncRNA content in other cells throughout the body under the transmission of exosomes, thereby inducing skeletal muscle mass loss and fat loss. A 2018 review innovatively summarized miRNAs that are dysregulated in various cachexia and cause skeletal muscle depletion and named ‘AtromiRs’ [ 41 ].So, we believe that there are also a series of ncRNAs that not only have dysregulated expression in a variety of cancers, but also cause fat loss.…”

The Pathway to Cancer Cachexia: MicroRNA-Regulated Networks in Muscle Wasting Based on Integrative Meta-Analysis

“…In fact, global gene expression studies of muscle wasting conditions, such as glucocorticoid treatment, immobilization, unloading, diabetes, sarcopenia, starvation, and denervation [22,23,24,25,26,27], have helped to shed light on the molecular mechanisms of muscle atrophy, including the identification of new potential biomarkers of cancer cachexia [28,29]. The identification of microRNAs has also broadened the knowledge about global gene expression regulation in conditions that induce skeletal muscle atrophy [30,31,32,33], including cancer cachexia [34,35]. However, there is a lack of integration of global microRNA and mRNA expression data from the same set of muscle samples in previous cancer cachexia studies [28,29,34,35,36,37,38,39,40,41].…”