Therapeutic Implications of miRNAs for Muscle-Wasting Conditions

Abstract

MicroRNAs (miRNAs) are small, non-coding RNA molecules that are mainly involved in translational repression by binding to specific messenger RNAs. Recently, miRNAs have emerged as biomarkers, relevant for a multitude of pathophysiological conditions, and cells can selectively sort miRNAs into extracellular vesicles for paracrine and endocrine effects. In the overall context of muscle-wasting conditions, a multitude of miRNAs has been implied as being responsible for the typical dysregulation of anabolic and catabolic pathways. In general, chronic muscle disorders are associated with the main characteristic of a substantial loss in muscle mass. Muscular dystrophies (MDs) are a group of genetic diseases that cause muscle weakness and degeneration. Typically, MDs are caused by mutations in those genes responsible for upholding the integrity of muscle structure and function. Recently, the dysregulation of miRNA levels in such pathological conditions has been reported. This revelation is imperative for both MDs and other muscle-wasting conditions, such as sarcopenia and cancer cachexia. The expression levels of miRNAs have immense potential for use as potential diagnostic, prognostic and therapeutic biomarkers. Understanding the role of miRNAs in muscle-wasting conditions may lead to the development of novel strategies for the improvement of patient management.

Effect of miR-144-3p-Targeted Regulation of PTEN on Proliferation, Apoptosis, and Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells under Stretch

“…miRNAs are endogenous noncoding RNAs that regulate the expression of target genes mainly at the transcriptional or posttranscriptional level and play important roles in a variety of life events. Recent studies have shown that miRNAs are involved in the regulation of MSC proliferation, lipogenesis, and osteogenic differentiation or apoptosis and play an important role in the fate determination of MSCs [ 14 , 15 ]. It has been reported [ 16 ] that miR-144-3p may be involved in the regulation of osteogenic differentiation and proliferation process of mouse MSCs.…”

The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

“…Another hot topic of applying exosomal cargo for muscle healing is the treatment of Duchenne muscular dystrophy [ 26 , 133 , 134 ]. The transfer of SOD1 and SOD3, or myostatin propeptide through exosomes can replace the mutated SOD1, and accelerate muscle regeneration [ 26 , 133 ].…”

Shared and Divergent Epigenetic Mechanisms in Cachexia and Sarcopenia

“…miR-147-3p, miR-299-3p, miR-1933-3p, miR-511-3p, miR-3473d, miR-665-3p, and miR-205-3p were found to be dysregulated. These miRNAs are associated with crucial cellular processes, such as cell-to-cell communication, development, growth, and inflammatory response [ 118 , 119 ]. Notably, miR-205 has been also found to be upregulated in different types of cancer, such as colorectal cancer and nasopharyngeal cancer.…”

“…In adult skeletal muscle, miR-205 plays a crucial role in proteasomal degradation, thereby altering muscle proteostasis in a negative manner. Indeed, it was predicted that miR-205 targets the MYC proto-oncogene, bHLH transcription factor (MYC), thus leading to the inhibition of AKT and cascade activation of E3 ligases, atrogin-1/muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MurF-1), the main mediators of muscle protein degradation in cachexia [ 110 , 119 ]. Furthermore, CREB1 is also targeted by miR-450a-5p and was found to be upregulated in skeletal muscles of cachectic non-small-cell lung carcinoma (NSCLC) patients.…”