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A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition.
Bracken, Cameron P; Gregory, Philip A; Kolesnikoff, Natasha; Bert, Andrew G; Wang, Jun; Shannon, M Frances; Goodall, Gregory J.
Afiliación
  • Bracken CP; Hanson Institute, Institute of Medical and Veterinary Science, The University of Adelaide, Adelaide, SA, Australia.
Cancer Res ; 68(19): 7846-54, 2008 Oct 01.
Article en En | MEDLINE | ID: mdl-18829540
Epithelial to mesenchymal transition occurs during embryologic development to allow tissue remodeling and is proposed to be a key step in the metastasis of epithelial-derived tumors. The miR-200 family of microRNAs plays a major role in specifying the epithelial phenotype by preventing expression of the transcription repressors, ZEB1/deltaEF1 and SIP1/ZEB2. We show here that miR-200a, miR-200b, and the related miR-429 are all encoded on a 7.5-kb polycistronic primary miRNA (pri-miR) transcript. We show that the promoter for the pri-miR is located within a 300-bp segment located 4 kb upstream of miR-200b. This promoter region is sufficient to confer expression in epithelial cells and is repressed in mesenchymal cells by ZEB1 and SIP1 through their binding to a conserved pair of ZEB-type E-box elements located proximal to the transcription start site. These findings establish a double-negative feedback loop controlling ZEB1-SIP1 and miR-200 family expression that regulates cellular phenotype and has direct relevance to the role of these factors in tumor progression.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas de Unión al ARN / Proteínas de Homeodominio / Retroalimentación Fisiológica / MicroARNs / Células Epiteliales / Mesodermo / Proteínas del Tejido Nervioso Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cancer Res Año: 2008 Tipo del documento: Article País de afiliación: Australia

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas de Unión al ARN / Proteínas de Homeodominio / Retroalimentación Fisiológica / MicroARNs / Células Epiteliales / Mesodermo / Proteínas del Tejido Nervioso Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cancer Res Año: 2008 Tipo del documento: Article País de afiliación: Australia
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