Jianxin Tao1, Liping Shi1, Longchang Huang1, Haoze Shi1, Hang Chen1, Yixin Wang1, Tong Wang2. 1. Department of Endoscopy Surgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, People's Republic of China. 2. Department of Endoscopy Surgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, 214023, People's Republic of China. aanti@163.com.
Abstract
PURPOSE: Transforming growth factor-β (TGF-β) induction of epithelial-mesenchymal transition (EMT) in SW480 was established as a system for studies of colon cancer metastasis. However, the epigenetic mechanisms underlying this process remain unknown. In mammal, polycomb repressive complex-2 (PRC2) is a highly conserved histone methyltransferase involved in epigenetic regulations. Enhancer of zeste Homolog 2 (EZH2) is the catalytic subunit of PRC2, which catalyzes methylation of lysine 27 of histone H3 (H3K27). METHODS: An inducible EMT system in colorectal cancer was utilized to study its mechanistic and phenotypic changes. Particularly, gene expression analysis was studied after immunoprecipitation. RESULTS: In this study, we reported that EZH2 is significantly enriched in the promoter region of WNT5A after TGF-β induction in SW480 colon cancer cell line, which in turn silenced the expression of WNT5A. Furthermore, EZH2 inhibitor antagonized the TGF-β-induced morphological conversion associated with epithelial-mesenchymal transition (EMT). Conversely, inhibition of histone H3K27me3 reader CBX does not affect the WNT5A expression level during TGF-β-induced EMT. CONCLUSIONS: Our results indicate that EZH2 was essential for the silencing of WNT5A during TGF-β-induced epithelial-mesenchymal transition of colon cancer cells.
PURPOSE: Transforming growth factor-β (TGF-β) induction of epithelial-mesenchymal transition (EMT) in SW480 was established as a system for studies of colon cancer metastasis. However, the epigenetic mechanisms underlying this process remain unknown. In mammal, polycomb repressive complex-2 (PRC2) is a highly conserved histone methyltransferase involved in epigenetic regulations. Enhancer of zeste Homolog 2 (EZH2) is the catalytic subunit of PRC2, which catalyzes methylation of lysine 27 of histone H3 (H3K27). METHODS: An inducible EMT system in colorectal cancer was utilized to study its mechanistic and phenotypic changes. Particularly, gene expression analysis was studied after immunoprecipitation. RESULTS: In this study, we reported that EZH2 is significantly enriched in the promoter region of WNT5A after TGF-β induction in SW480 colon cancer cell line, which in turn silenced the expression of WNT5A. Furthermore, EZH2 inhibitor antagonized the TGF-β-induced morphological conversion associated with epithelial-mesenchymal transition (EMT). Conversely, inhibition of histone H3K27me3 reader CBX does not affect the WNT5A expression level during TGF-β-induced EMT. CONCLUSIONS: Our results indicate that EZH2 was essential for the silencing of WNT5A during TGF-β-induced epithelial-mesenchymal transition of colon cancer cells.
Entities:
Keywords:
Enhancer of zeste Homolog 2; Epithelial to mesenchymal transition; Histone 3 lysine 27 trimethylation; Transforming growth factor-β; WNT signaling
Authors: Maria S Pino; Hirotoshi Kikuchi; Min Zeng; Maria-Teresa Herraiz; Isabella Sperduti; David Berger; Do-Youn Park; A John Iafrate; Lawrence R Zukerberg; Daniel C Chung Journal: Gastroenterology Date: 2009-12-21 Impact factor: 22.682
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