A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition

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dc.contributor.authorBracken, C.
dc.contributor.authorGregory, P.
dc.contributor.authorKolesnikoff, N.
dc.contributor.authorBert, A.
dc.contributor.authorWang, J.
dc.contributor.authorShannon, M.
dc.contributor.authorGoodall, G.
dc.date.issued2008
dc.description.abstractEpithelial 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/delta EF1 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.
dc.description.statementofresponsibilityCameron P. Bracken, Philip A. Gregory, Natasha Kolesnikoff, Andrew G. Bert, Jun Wang, M. Frances Shannon, and Gregory J. Goodall
dc.identifier.citationCancer Research, 2008; 68(19):7846-7854
dc.identifier.doi10.1158/0008-5472.CAN-08-1942
dc.identifier.issn0008-5472
dc.identifier.issn1538-7445
dc.identifier.orcidGregory, P. [0000-0002-0999-0632]
dc.identifier.orcidGoodall, G. [0000-0003-1294-0692]
dc.identifier.urihttp://hdl.handle.net/2440/48450
dc.language.isoen
dc.publisherAmerican Association for Cancer Research
dc.rights©2008 American Association for Cancer Research.
dc.source.urihttps://doi.org/10.1158/0008-5472.can-08-1942
dc.subjectmicroRNA; transcription; ZEB; feedback; epithelial-mesenchymal transition
dc.titleA double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition
dc.typeJournal article
pubs.publication-statusPublished

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