Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/52411
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Type: Journal article
Title: The mir-200 family and mir-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1
Author: Gregory, P.
Bert, A.
Paterson, E.
Barry, S.
Tsykin, A.
Farshid, G.
Vadas, M.
Khew-Goodall, Y.
Goodall, G.
Citation: Nature Cell Biology, 2008; 10(5):593-601
Publisher: Nature Publishing Group
Issue Date: 2008
ISSN: 1465-7392
1476-4679
Statement of
Responsibility: 
Philip A. Gregory, Andrew G. Bert, Emily L. Paterson, Simon C. Barry, Anna Tsykin, Gelareh Farshid, Mathew A. Vadas, Yeesim Khew-Goodall and Gregory J. Goodall
Abstract: Epithelial to mesenchymal transition (EMT) facilitates tissue remodelling during embryonic development and is viewed as an essential early step in tumour metastasis. We found that all five members of the microRNA-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) and miR-205 were markedly downregulated in cells that had undergone EMT in response to transforming growth factor (TGF)- or to ectopic expression of the protein tyrosine phosphatase Pez. Enforced expression of the miR-200 family alone was sufficient to prevent TGF--induced EMT. Together, these microRNAs cooperatively regulate expression of the E-cadherin transcriptional repressors ZEB1 (also known as EF1) and SIP1 (also known as ZEB2), factors previously implicated in EMT and tumour metastasis. Inhibition of the microRNAs was sufficient to induce EMT in a process requiring upregulation of ZEB1 and/or SIP1. Conversely, ectopic expression of these microRNAs in mesenchymal cells initiated mesenchymal to epithelial transition (MET). Consistent with their role in regulating EMT, expression of these microRNAs was found to be lost in invasive breast cancer cell lines with mesenchymal phenotype. Expression of the miR-200 family was also lost in regions of metaplastic breast cancer specimens lacking E-cadherin. These data suggest that downregulation of the microRNAs may be an important step in tumour progression.
Keywords: Epithelium
Cell Line
Mesoderm
Animals
Dogs
Humans
Breast Neoplasms
Neoplasm Invasiveness
Actins
RNA-Binding Proteins
Homeodomain Proteins
Cadherins
Membrane Proteins
Nerve Tissue Proteins
Phosphoproteins
Transcription Factors
MicroRNAs
RNA, Small Interfering
Microarray Analysis
Phenotype
Genes, Reporter
Female
Transforming Growth Factor beta1
Zonula Occludens-1 Protein
Zinc Finger E-box-Binding Homeobox 1
Description: © 2008 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
DOI: 10.1038/ncb1722
Appears in Collections:Aurora harvest
Paediatrics publications

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