Dysregulation of MicroRNA Expression in Myotonic Dystrophies

Myotonic dystrophies (DM) are dominantly inherited multisystemic disorders affecting skeletal muscle, heart, eye, and the endocrine system. Myotonic dystrophy type-1 (DM1) is caused by expansion of a CTG repeat in the 3’UTR of DMPK gene, while myotonic dystrophy type-2 (DM2) is caused by expansion of a CCTG repeat in the intron 1 of ZNF9 gene. Both amplifications lead to the production of mutant mRNA transcripts which interfere with alternative splicing of other genes. However, other molecular mechanisms may be involved in DM pathogenesis. MicroRNAs (miRNAs) are short non-coding RNAs regulating gene expression at post-trascriptional level. Recently, dysregulation of miRNAs expression has been correlated with several muscle diseases. However, miRNAs levels have not been studied in DM. We measured the expression of 24 miRNAs in muscle biopsies of DM1 (n 15), DM2 (n 9) and control (n 10) subjects. Upregulation of miR1 and miR335 and downregulation of miR29b, miR29c, miR33 and miR223 was observed in DM1 biopsies. In DM2 biopsies, upregulation of miR34c was identified. Moreover tissue distribution of selected miRNAs was determined by in situ hybridization. This initial screening shows that miRNAs are differentially expressed in DM, suggesting their potential role in DM pathogenesis.