The common microRNA signatures associated with mitochondrial dysfunction in different muscular dystrophies.

Secondary mitochondrial damage in skeletal muscles is a common feature of different neuromuscular disorders (NMD), which fall outside the mitochondrial cytopathies. The common cause of mitochondrial dysfunction and structural changes in skeletal muscle tissue remains to be discovered. Although they are associated with different clinical, genetic, and pathological backgrounds, the pathomechanisms underlying NMDs might be attributed to the complex interaction and crosstalk between mitochondria and the associated microRNAs (miRNAs). In this study, we aimed to identify the common miRNA signatures that are associated with mitochondrial damage in different muscular dystrophies (MDs) [Duchenne Muscular Dystrophy (DMD), Megaconial Congenital Muscular Dystrophy (CMD), Ullrich CMD (UCMD), and alpha-dystroglycanopathy (αDGpathy)]. We analyzed the miRnome profiles of skeletal muscle biopsies acquired from four different MD groups and control individuals by miRNA microarray. We identified 17 common upregulated miRNAs in all the tested MD groups. A specific bioinformatics approach identified 10 of these miRNAs to be specifically related to the mitochondrial pathways. Six miRNAs, miR-134-5p, miR-199a-5p, miR-382-5p, miR-409-3p, miR-497-5p, and miR-708-5p, were associated with the top four mitochondrial pathways and were thus selected as priority candidates for further validation by quantitative Real-Time PCR analysis. We demonstrate, for the first time, common upregulated miRNAs that are associated with mitochondrial damage in different MD groups, therefore, contributing to the pathophysiology. Our findings may open a new gate towards therapeutics.