Myotonic dystrophy type 1(DM1) is a dominantly inherited multisystemic disorder affecting skeletal muscle, heart, eye, and the endocrine system. DM1 is caused by expansion of a CTG repeat in the 3’UTR of DMPK gene. This genetic lesion leads to the accumulation of the expanded CUG transcripts into discrete nuclear RNA foci which interfere with alternative splicing of other genes. However, other molecular mechanisms may be involved in DM1 pathogenesis. MicroRNAs (miRNAs) are short non-coding RNAs that regulate the stability and/or the translational efficiency of target messenger RNAs. Recently, several studies have demonstrated that microRNA expression is disrupted in several myopathies such as Duchenne, Becker, facioscapulohumeral muscular dystrophies and DM1. The aim of this study is to assay whether levels and cellular localization of a group of candidate miRNAs is altered in DM1 patients, potentially contributing to DM1 pathogenetic mechanisms. We have analysed the expression of 24 specific miRNAs by TaqMan Real Time PCR (qPCR) method on muscle biopsies from DM1 (n=15) and control (n=10) subjects. We found that miR-1 and miR-335 are up-regulated, whereas miR-29b and c, and miR-33 are downregulated in DM1 biopsies compared to controls. In order to assess whether miRNA deregulation is functionally relevant, we have examined the impact of the identified miRNAs deregulation on the expression of their potential target genes in DM1 patients. Potential targets analysis by qPCR shows that both miR-29 and miR-1 targets are significantly up-regulated. Moreover the cellular localization of the identified miRNAs has been assayed by in situ hybridization on cryostat muscle sections derived from 5 DM1 and control biopsies. The cellular distribution of muscle specific miR-1, miR-133b and miR-206 appears to be severely altered in DM1 skeletal muscles. Our results indicate that the observed miRNA dysregulations and myslocalizations may contribute to DM1 pathogenetic mechanisms.
|Titolo:||Dysregulated expression of micrornas in myotonic dystrophy type 1|
MEOLA, GIOVANNI (Penultimo)
|Data di pubblicazione:||mag-2011|
|Parole Chiave:||Dysregulated expression ; micrornas ; myotonic dystrophy type 1|
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
|Citazione:||Dysregulated expression of micrornas in myotonic dystrophy type 1 / R. Cardani, S. Greco, G. Sarra-Ferraris, E. Bugiardini, G. Meola, F. Martelli. ((Intervento presentato al 4. convegno International Congress of Myology tenutosi a Lille nel 2011.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|