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- W2313521504 abstract "Epithelial - mesenchymal transition (EMT) is a physiological process in normal tissue development and wound healing that has been shown to play important roles in tumor metastasis, “stemness,” and drug resistance. Therefore, it is critical to understand the molecular mechanisms that control EMT. EMT is typically characterized by the loss of the epithelial marker E-cadherin and gain of the transcriptional repressors of E-cadherin (Zeb1, Zeb2, Twist, SnaiI, and Slug). MicroRNAs belonging to the mir200 family and miR205 are involved in EMT through suppression of Zeb1 and Zeb2. Recently, p53 has been demonstrated to regulate EMT by transcriptionally activating the microRNA mir-200c, which in turn suppresses Zeb1; however, the mechanisms controlling miR205 remain elusive. We noticed that expression of the p53 homologue p63 correlates with the expression of E-cadherin in bladder cancer cell lines, suggesting that p63 might participate in regulating EMT. Consistent with this idea, expression of p63 and miR205 are strongly correlated with each other in a large panel of bladder cancer cell lines. Interestingly, stably knocking down (KD) p63 in two epithelial cell lines (UM-UC6 and UM-UC14) repressed the expression of miR205. Consistent with the role of miR205 in suppressing Zeb1, p63 knockdown resulted in increased expression of Zeb1 in the UM-UC6 cells, and this effect was reversed by expression of exogenous miR205. p63 knockdown reduced both the primary and mature forms of miR205, suggesting that p63 might transcriptionally activate miR205 gene expression. Intriguingly, chromatin immunoprecipitation (ChIP) revealed that p63 binds to a putative regulatory region of miR205 in UM-UC6 and UM-UC14. Furthermore, the acetylated histone H3 mark (indicative of active/open chromatin) was enriched in the region encompassing the p63 binding site. Together, our data identifies p63 as an important repressor of EMT via its ability to promote expression of miR205, which represses Zeb1 expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-472. doi:1538-7445.AM2012-LB-472" @default.
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- W2313521504 date "2012-04-15" @default.
- W2313521504 modified "2023-09-27" @default.
- W2313521504 title "Abstract LB-472: p63 inhibits epithelial - mesenchymal transition by promoting the expression of miR205 in human bladder cancer cells" @default.
- W2313521504 doi "https://doi.org/10.1158/1538-7445.am2012-lb-472" @default.
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