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Medical Oncology

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01.03.2016 | Original Paper

Epigenetic regulation of E-cadherin expression by the histone demethylase UTX in colon cancer cells

verfasst von: Lin Zha, Qiang Cao, Xin Cui, Fenfen Li, Houjie Liang, Bingzhong Xue, Hang Shi

Erschienen in: Medical Oncology | Ausgabe 3/2016

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Abstract

Decreased epithelial cadherin (E-cadherin) gene expression, a hallmark of epithelial–mesenchymal transition (EMT), is essential for triggering metastatic advantage of the colon cancer. Genetic mechanisms underlying the regulation of E-cadherin expression in EMT have been extensively investigated; however, much is unknown about the epigenetic mechanism underlying this process. Here, we identified ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX), a histone demethylase involved in demethylating di- or tri-methylated histone 3 lysine 27 (H3K27me2/3), as a positive regulator for the expression of E-cadherin in the colon cancer cell line HCT-116. We showed that inactivation of UTX down-regulated E-cadherin gene expression, while overexpression of UTX did the opposite. Notably, overexpression of UTX inhibited migration and invasion of HCT-116 cells. Moreover, UTX demethylated H3K27me3, a histone transcriptional repressive mark, leading to decreased H3K27me3 at the E-cadherin promoter. Further, UTX interacted with the histone acetyltransferase (HAT) protein CBP and recruited it to the E-cadherin promoter, resulting in increased H3K27 acetylation (H3K27ac), a histone transcriptional active mark. UTX positively regulates E-cadherin expression through coordinated regulation of H3K27 demethylation and acetylation, switching the transcriptional repressive state to the transcriptional active state at the E-cadherin promoter. We conclude that UTX may play a role in regulation of E-cadherin gene expression in HCT-116 cells and that UTX may serve as a therapeutic target against the metastasis in the treatment of colon cancer.

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Titel: Epigenetic regulation of E-cadherin expression by the histone demethylase UTX in colon cancer cells
verfasst von: Lin Zha
Qiang Cao
Xin Cui
Fenfen Li
Houjie Liang
Bingzhong Xue
Hang Shi
Publikationsdatum: 01.03.2016
Verlag: Springer US
Erschienen in: Medical Oncology / Ausgabe 3/2016
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-016-0734-z

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Epigenetic regulation of E-cadherin expression by the histone demethylase UTX in colon cancer cells

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