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

Am J Pathol. 2020 Oct;190(10):2136-2145. doi: 10.1016/j.ajpath.2020.06.011. Epub 2020 Jul 7.


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 α-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, 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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Computational Biology / methods
  • Female
  • Gene Expression Profiling / methods
  • Humans
  • Infant
  • Male
  • MicroRNAs / genetics
  • Mitochondria / metabolism*
  • Muscle, Skeletal / pathology*
  • Muscular Dystrophies / genetics*
  • Muscular Dystrophy, Duchenne / genetics*
  • Sclerosis / genetics*


  • MicroRNAs

Supplementary concepts

  • Scleroatonic muscular dystrophy