EZH2 is involved in silencing of WNT5A during epithelial-mesenchymal transition of colon cancer cell line.

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.