title: A core microRNA signature associated with inducers of the epithelial-to-mesenchymal transition.
abstract: Although it is becoming clear that certain miRNAs fulfil a fundamental role in the regulation of the epithelial-to-mesenchymal transition (EMT), a comprehensive study of the miRNAs associated with this process has yet to be performed. Here, we profiled the signature of miRNA expression in an in vitro model of EMT, ectopically expressing in MDCK cells one of seven EMT transcription factors (SNAI1, SNAI2, ZEB1, ZEB2, TWIST1, TWIST2 or E47) or the EMT inducer LOXL2. In this way, we identified a core subset of deregulated miRNAs that were further validated in vivo, studying endometrial carcinosarcoma (ECS), a tumour entity that represents an extreme example of phenotypic plasticity. Moreover, epigenetic silencing through DNA methylation of miRNA genes of the miR-200 family and miR-205 that are down-regulated during EMT was evident in both the in vitro (MDCK transfectants) and in vivo (ECS) models of EMT. The strong correlation between expression and DNA methylation suggests a major role for this epigenetic mark in the regulation of the miR-141-200c locus.
authors.affiliation: Department of Pathology, Instituto de Biomedicina de Sevilla, CSIC-Universidad de Sevilla, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Díaz-Martín
authors.forename: Antonio
authors.initials: A
authors.lastname: Díaz-López
authors.forename: Gema
authors.initials: G
authors.lastname: Moreno-Bueno
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: Castilla
authors.forename: Juan M
authors.initials: JM
authors.lastname: Rosa-Rosa
authors.forename: Amparo
authors.initials: A
authors.lastname: Cano
authors.forename: José
authors.initials: J
authors.lastname: Palacios
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002296:Carcinosarcoma / Q000235:genetics*; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics; D004285:Dogs; D016889:Endometrial Neoplasms / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000235:genetics*; D014162:Transfection
chemical_list: D035683:MicroRNAs
keywords: DNA methylation; EMT; endometrial carcinosarcoma; miRNA