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https://hdl.handle.net/2440/48450
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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. |
DOI: | 10.1158/0008-5472.CAN-08-1942 |
Published version: | http://dx.doi.org/10.1158/0008-5472.can-08-1942 |
Appears in Collections: | Aurora harvest Medicine publications |
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