Bracken, C.Gregory, P.Kolesnikoff, N.Bert, A.Wang, J.Shannon, M.Goodall, G.2008-11-202008-11-202008Cancer Research, 2008; 68(19):7846-78540008-54721538-7445http://hdl.handle.net/2440/48450Epithelial 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.en©2008 American Association for Cancer Research.microRNA; transcription; ZEB; feedback; epithelial-mesenchymal transitionJournal article002008303810.1158/0008-5472.CAN-08-19420002600299000202-s2.0-5404908438041724Gregory, P. [0000-0002-0999-0632]Goodall, G. [0000-0003-1294-0692]