MyomiRs Expression in Limb Girdle Muscular Dystrophy

ABSTRACT This manuscript is a comprehensive review focused on the role of microRNAs (miRs)—short RNA molecules—in Limb Girdle Muscular Dystrophy (LGMD). LGMD encompasses various and heterogeneous rare genetic neuromuscular diseases, characterized by the progressive wasting and deterioration of muscle fibers, predominantly affecting the pelvic and shoulder girdles. Similar to other muscular dystrophies, LGMD exhibits a dysregulated expression of miRs that are crucial for gene expression regulation and cellular processes. Notably, myomiRNAs, which are preferentially expressed in muscle tissue and linked to muscle cell proliferation and differentiation, appear to be particularly affected. Numerous studies have aimed to identify differentially expressed miRNAs in both physiological and pathological conditions with different purposes: (a) the identification of molecular markers for diagnostic and prognostic purposes, and for evaluation of the effects of possible therapeutic strategies; (b) the detection of a molecular signature to differentiate both LGMD from other muscular dystrophies and LGMD subtypes from each other. The main conclusions so far emerged from published studies are: (a) a high number of differentially expressed miRs have been found in both the serum and muscle fibers of LGMD patients (canonical myomiRNAs, including miR‐1, miR‐133a/b, and miR‐206, are frequently found to be dysregulated across various LGMD subtypes); (b) circulating levels of miR‐206 were found to be significantly elevated in LGMD patients compared to healthy subjects and have been suggested as a potential biomarker of general muscle damage in various muscular dystrophies; (c) possible identification of subtype‐specific molecular signatures (for instance, the combination of six specific miRs has been proposed to discriminate LGMD patients from controls and to identify particular LGMD subtypes, such as LGMDR1, LGMDR2, LGMDR3, and LGMDR4); (d) currently not validated miRNA biomarkers have been described for clinical use yet in LGMD due to heterogeneity of published studies (regarding the type of biological material and techniques used) and limited number of involved patients. Therefore, while miRs show great promise for improving the molecular understanding, stratification, and management of LGMD patients, further rigorous research and validation in larger, standardized patient cohorts are necessary to confirm the clinical reliability of these identified miRNAs.