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.
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Acknowledgements
This work was supported by grants from Health and Family Planning Commission of Wuxi (#ZDXK008), the National Natural Sciences Foundation of China (No. 81371683/H1819), Clinical Medicine Project of Jiangsu Province (BL2014023).
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Tao, J., Shi, L., Huang, L. et al. EZH2 is involved in silencing of WNT5A during epithelial–mesenchymal transition of colon cancer cell line. J Cancer Res Clin Oncol 143, 2211–2219 (2017). https://doi.org/10.1007/s00432-017-2479-2
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DOI: https://doi.org/10.1007/s00432-017-2479-2