deregulated micrornas in myotonic dystrophy type 2解除肌强直性营养不良2型小分子核糖核酸.pdfVIP

Deregulated MicroRNAs in Myotonic Dystrophy Type 2 1. 1. 3 1 3 Simona Greco , Alessandra Perfetti , Pasquale Fasanaro , Rosanna Cardani , Maurizio C. Capogrossi , 1,2 1 Giovanni Meola , Fabio Martelli * 1 IRCCS-Policlinico San Donato, Milan, Italy, 2 University of Milan, Milan, Italy, 3 Istituto Dermopatico dell’Immacolata-IRCCS, Rome, Italy Abstract Myotonic Dystrophy Type-2 (DM2) is an autosomal dominant disease caused by the expansion of a CCTG tetraplet repeat. It is a multisystemic disorder, affecting skeletal muscles, the heart, the eye, the central nervous system and the endocrine system. Since microRNA (miRNA) expression is disrupted in Myotonic Dystrophy Type-1 and many other myopathies, miRNAs deregulation was studied in skeletal muscle biopsies of 13 DM2 patients and 13 controls. Eleven miRNAs were deregulated: 9 displayed higher levels compared to controls (miR-34a-5p, miR-34b-3p, miR-34c-5p, miR-146b-5p, miR-208a, miR-221-3p and miR-381), while 4 were decreased (miR-125b-5p, miR-193a-3p, miR-193b-3p and miR-378a-3p). To explore the relevance of DM2 miRNA deregulation, the predicted interactions between miRNA and mRNA were investigated. Global gene expression was analyzed in DM2 and controls and bioinformatic analysis identified more than 1,000 miRNA/mRNA interactions. Pathway and function analysis highlighted the involvement of the miRNA-deregulated mRNAs in multiple aspects of DM2 pathophysiology. In conclusion, the observed miRNA dysregulations may contribute to DM2 pathogenetic mechanisms. Citation: Greco S, Perfetti A, Fasanaro P, Cardani R, Capogrossi MC, et al. (2012) Deregulat