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/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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Bracken CP,Gregory PA,Kolesnikoff N,Bert AG,Wang J,Shannon MF,Goodall GJdoi
10.1158/0008-5472.CAN-08-1942subject
Has Abstractpub_date
2008-10-01 00:00:00pages
7846-54issue
19eissn
0008-5472issn
1538-7445pii
68/19/7846journal_volume
68pub_type
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