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

Autor: Díaz-Martín, J., Díaz-Lopez, Antonio, Moreno-Bueno, Gema, Castilla, María Ángeles, Rosa-Rosa, Juan M., Cano, Amparo, Palacios Calvo, José
Přispěvatelé: Junta de Andalucía, Ministerio de Economía y Competitividad (España), European Commission, Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Asociación Española Contra el Cáncer, Comunidad de Madrid
Rok vydání: 2014
Předmět:
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
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ISSN: 1096-9896
0022-3417
Popis: 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.
This work was supported by the Instituto de Salud Carlos III (ISCIII; Grant No. PI080971 to JP) and the Ministerio de Ciencia e Innovación (MICINN), co-financed by the European Development Regional Fund (Grant No. RD06/0020/0013 to JP), the Junta de Andalucía (Consejería de Salud; Grant Nos PI-0384/2007 and PI0581/2009, to JP), MICINN (Grant No. SAF-2010-21143; Consolider-Ingenio Grant No. CSD2007-00017 to AC; Grant No. SAF2010-20175 to GMB), Comunidad de Madrid (Grant No.S2010/BMD-2303, to AC and GMB), Asociación Española Contra el Cáncer (Grant No. AECC 2011, to GMB) and ISCIII-Ministerio de Economía y Competitividad (MINECO; Grant No. RD12/0036/0064 to JP; Grant No. RD12/0036/0007 to AC). JDM is a PhD researcher funded by the Consejería de Salud, Junta de Andalucía (Grant No. PI0581/2009). MAC and ADL are PhD researchers funded by the ISCIII (Grant No. RD06/0020/0013 and Sara Borrell contracts, respectively).
Databáze: OpenAIRE
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