The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1.

@article{citeulike:2621879, 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)-beta or to ectopic expression of the protein tyrosine phosphatase Pez. Enforced expression of the miR-200 family alone was sufficient to prevent TGF-beta-induced EMT. Together, these microRNAs cooperatively regulate expression of the E-cadherin transcriptional repressors ZEB1 (also known as deltaEF1) 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.}, address = {[1] Hanson Institute and Division of Human Immunology, Institute of Medical and Veterinary Science, Adelaide, SA 5000, Australia. [2] Discipline of Medicine, The University of Adelaide, Adelaide, SA 5005, Australia.}, author = {Gregory, Philip A A. and Bert, Andrew G G. and Paterson, Emily L L. and Barry, Simon C C. and Tsykin, Anna and Farshid, Gelareh and Vadas, Mathew A A. and Khew-Goodall, Yeesim and Goodall, Gregory J J. }, citeulike-article-id = {2621879}, doi = {10.1038/ncb1722}, issn = {1465-7392}, journal = {Nature cell biology}, month = {March}, posted-at = {2008-04-02 04:18:45}, priority = {2}, title = {The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1.}, url = {http://dx.doi.org/10.1038/ncb1722}, year = {2008} }

TY - JOUR ID - citeulike:2621879 L3 - citeulike-article-id:2621879 TI - The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. JF - Nature cell biology AD - [1] Hanson Institute and Division of Human Immunology, Institute of Medical and Veterinary Science, Adelaide, SA 5000, Australia. [2] Discipline of Medicine, The University of Adelaide, Adelaide, SA 5005, Australia. SN - 1465-7392 N2 - 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)-beta or to ectopic expression of the protein tyrosine phosphatase Pez. Enforced expression of the miR-200 family alone was sufficient to prevent TGF-beta-induced EMT. Together, these microRNAs cooperatively regulate expression of the E-cadherin transcriptional repressors ZEB1 (also known as deltaEF1) 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. AU - Gregory, Philip A AU - Bert, Andrew G AU - Paterson, Emily L AU - Barry, Simon C AU - Tsykin, Anna AU - Farshid, Gelareh AU - Vadas, Mathew A AU - Khew-Goodall, Yeesim AU - Goodall, Gregory J PY - 2008/03/30/ UR - http://dx.doi.org/10.1038/ncb1722 ER -