title: miR-186 inhibits muscle cell differentiation through myogenin regulation.
abstract: The complex process of skeletal muscle differentiation is organized by the myogenic regulatory factors (MRFs), Myf5, MyoD, Myf6, and myogenin, where myogenin plays a critical role in the regulation of the final stage of muscle differentiation. In an effort to investigate the role microRNAs (miRNAs) play in regulating myogenin, a bioinformatics approach was used and six miRNAs (miR-182, miR-186, miR-135, miR-491, miR-329, and miR-96) were predicted to bind the myogenin 3'-untranslated region (UTR). However, luciferase assays showed only miR-186 inhibited translation and 3'-UTR mutagenesis analysis confirmed this interaction was specific. Interestingly, the expression of miR-186 mirrored that of its host gene, ZRANB2, during development. Functional studies demonstrated that miR-186 overexpression inhibited the differentiation of C2C12 and primary muscle cells. Our findings therefore identify miR-186 as a novel regulator of myogenic differentiation.
authors.affiliation: From the Department of Molecular Genetics, Function, and Therapy, The Cyprus Institute of Neurology and Genetics, 1683, Nicosia, Cyprus and.
authors.forename: Antonis
authors.initials: A
authors.lastname: Antoniou
authors.forename: Nikolaos P
authors.initials: NP
authors.lastname: Mastroyiannopoulos
authors.forename: James B
authors.initials: JB
authors.lastname: Uney
authors.forename: Leonidas A
authors.initials: LA
authors.lastname: Phylactou
mesh_terms: D020413:3' Untranslated Regions / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D018008:Myogenin / Q000096:biosynthesis* / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C503801:Myog protein, mouse; D018008:Myogenin; D016601:RNA-Binding Proteins; C486374:Zranb2 protein, mouse
keywords: Differentiation; Gene Regulation; MicroRNA; Muscle; Myogenesis; Myogenin