A core microRNA signature associated with inducers of the epithelial-to-mesenchymal transition

作者：Diaz Martin Juan; Diaz Lopez Antonio; Moreno Bueno Gema; Angeles Castilla M; Rosa Rosa Juan M; Cano Amparo; Palacios Jose^*

来源：Journal of Pathology, 2014, 232(3): 319-329.

DOI：10.1002/path.4289

• EMT
• miRNA
• DNA methylation
• endometrial carcinosarcoma

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.

• 出版日期2014-2