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Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/48450

Type: Journal article
Title: A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition
Author: Bracken, C.
Gregory, P.
Kolesnikoff, N.
Bert, A.
Wang, J.
Shannon, M.
Goodall, G.
Citation: Cancer Research, 2008; 68(19):7846-7854
Publisher: American Association for Cancer Research
Issue Date: 2008
ISSN: 0008-5472
1538-7445
Statement of
Responsibility: 
Cameron P. Bracken, Philip A. Gregory, Natasha Kolesnikoff, Andrew G. Bert, Jun Wang, M. Frances Shannon, and Gregory J. Goodall
Abstract: 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/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.
Keywords: microRNA; transcription; ZEB; feedback; epithelial-mesenchymal transition
Rights: ©2008 American Association for Cancer Research.
RMID: 0020083038
DOI: 10.1158/0008-5472.CAN-08-1942
Appears in Collections:Medicine publications
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