The Common miRNA Signatures Associated with Mitochondrial Dysfunction in Different Muscular Dystrophies

Abstract

Secondary mitochondrial damage in skeletal muscles is a common feature of different neuromuscular disorders, 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 pathologic backgrounds, the pathomechanisms underlying neuromuscular disorders might be attributed to the complex interaction and cross talk between mitochondria and the associated miRNAs. This study aimed to identify the common miRNA signatures that are associated with mitochondrial damage in different muscular dystrophies (MDs; Duchenne muscular dystrophy, megaconial congenital muscular dystrophy, Ullrich congenital muscular dystrophy, and a-dystroglycanopathy). The miRNome profiles of skeletal muscle biopsies acquired from four different MD groups and control individuals were analyzed by miRNA microarray. We identified 17 common up-regulated miRNAs in all of the tested MD groups. A specific bioinformatics approach identified 10 of these miRNAs to be specifically related to the mitochondrial pathways. Six miRNAs,, 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 up-regulated miRNAs that are associated with mitochondrial damage in different MD groups, therefore contributing to the pathophysiology. Our findings may open a new gate toward therapeutics.

Secretory products from epicardial adipose tissue induce adverse myocardial remodeling after myocardial infarction by promoting reactive oxygen species accumulation

“…Through its suppression of KAT7 expression by binding to the 3’ UTR, miR-134-5p inhibited the KAT7-induced H3K14Ac of MnSOD and catalase, thereby decreasing the expressions of MnSOD and catalase and promoting ROS accumulation. In parallel with our study, Aksu-Menges et al [ 36 ] identified miR-134-5p as a commonly increased miRNA related to mitochondrial damage in patients with muscular dystrophy, thereby revealing a potential link between miR-134-5p and mitochondrial dysfunction.…”

The Profiling of 179 miRNA Expression in Serum from Limb Girdle Muscular Dystrophy Patients and Healthy Controls

“…In an in vitro model of murine myotubes, miRNA-328-5p silencing resulted in an induction of several genes involved in mitochondrial dynamics (MFN-1, MFN-2 and OPA-1) and biogenesis (SIRT1 and PGC-1α) and in the activation of the mitochondrial unfolded protein response [40]. Furthermore, miR-382-5p was associated with mitochondrial pathways related to different neuromuscular disorders [41]. Another interesting miRNA, down-regulated in LGMDR4, is miR-376c-3p.…”

Serum microRNAs in osteoporotic fracture and osteoarthritis: a genetic and functional study

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