title: Dysregulation and cellular mislocalization of specific miRNAs in myotonic dystrophy type 1.
abstract: Myotonic Dystrophy Type-1 (DM1) is caused by the expansion of a CTG repeat with a peculiar pattern of multisystemic involvement affecting skeletal muscles, the heart, the eye, the central nervous system and the endocrine system. Since microRNA expression is disrupted in several myopathies, the expression of 24 candidate microRNAs was analyzed in skeletal muscle biopsies of 15 DM1 patients. Controls were constituted by biopsies without overt pathological features derived from 14 subjects with suspected neuromuscular disorder of undetermined nature. We found that miR-1 and miR-335 were up-regulated, whereas miR-29b and c, and miR-33 were down-regulated in DM1 biopsies compared to controls. We also found that the cellular distribution of muscle specific miR-1, miR-133b and miR-206 was severely altered in DM1 skeletal muscles. MicroRNA dysregulation was likely functionally relevant, since it impacted on the expression of the predicted miR-1, and miR-29 targets. The observed miRNA dysregulations and myslocalizations may contribute to DM1 pathogenetic mechanisms.
authors.affiliation: Molecular Cardiology Laboratory, IRCCS-Policlinico San Donato, 20097 Milan, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Perbellini
authors.forename: Simona
authors.initials: S
authors.lastname: Greco
authors.forename: Gianluca
authors.initials: G
authors.lastname: Sarra-Ferraris
authors.forename: Rosanna
authors.initials: R
authors.lastname: Cardani
authors.forename: Maurizio C
authors.initials: MC
authors.lastname: Capogrossi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Meola
authors.forename: Fabio
authors.initials: F
authors.lastname: Martelli
mesh_terms: D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D020967:Myotonic Disorders / Q000378:metabolism / Q000473:pathology; D009223:Myotonic Dystrophy / Q000378:metabolism / Q000503:physiopathology; D009468:Neuromuscular Diseases / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology*; D055815:Young Adult
chemical_list: C544547:MIRN1 microRNA, human; C548234:MIRN133 microRNA, human; C546087:MIRN206 microRNA, human; C532045:MIRN29a microRNA, human; C556347:MIRN335 microRNA, human; C550416:MIRN33a microRNA, human; D035683:MicroRNAs