microRNA-mRNA expression profiles in the skeletal muscle of myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults, yet there are currently no disease-modifying treatments. Disrupted miRNA expressions may lead to dysregulation of target mRNAs and dysfunction involved in DM1 pathogenic mechanism. We used microarray platforms to examine the miRNA/mRNA expression profiles in skeletal muscle biopsies derived from DM1 patients and matched controls. Bioinformatics analysis and dual-luciferase reporter assay were conducted to provide insight into miRNA-mRNA regulatory networks altered in DM1. Twenty-three differentially expressed miRNAs and 135 differentially expressed genes were identified. qPCR confirmed that miR-3201, myogenic factor 5 (MYF5), myogenic differentiation 1 (MYOD1), CUGBP, Elav-like family member 1 (CELF1), and CELF2 were significantly up-regulated, while miR-196a, miR-200c, and miR-146a were significantly down-regulated. Enriched functions and pathways such as multicellular organismal development, RNA splicing, cell differentiation, and spliceosome are relevant to DM1. The miRNA-mRNA interaction network revealed that miR-182, miR-30c-2, and miR-200c were the critical nodes that potentially interacted with hub genes. Luciferase reporter assay confirmed the direct interaction between miR-196a and CELF2. Those results implied that the observed miRNA/mRNA dysregulation could contribute to specific functions and pathways related to DM1 pathogenesis, highlighting the dysfunction of miR-196a and CELF2.