Premium
A core microRNA signature associated with inducers of the epithelial‐to‐mesenchymal transition
Author(s) -
DíazMartín Juan,
DíazLópez Antonio,
MorenoBueno Gema,
Castilla M Ángeles,
RosaRosa Juan M,
Cano Amparo,
Palacios José
Publication year - 2014
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.4289
Subject(s) - epigenetics , dna methylation , microrna , biology , gene silencing , snai1 , epithelial–mesenchymal transition , methylation , microbiology and biotechnology , reprogramming , cancer research , genetics , transition (genetics) , gene expression , gene
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. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.