EZH2-mediated regulation of NF-κB target gene expression in gastric cancer / 中国病理生理杂志

ABSTRACT

AIM:To explore the mechanism by which over-expression of enhancer of zeste homolog 2 (EZH2) in a panel of gastric cancer cell lines is involved in tumorigenesis of gastric cancer .METHODS: Real-time PCR and Western blot were employed to examine the mRNA and protein levels of EZH 2, respectively.MTS assay, cell migration and soft agar assay were performed to investigate the role of EZH 2 in the regulation of stomach cancer behaviors .The effect of EZH2 on NF-κB target gene expression was determined by Luciferase reporter and real-time PCR.Co-immunoprecipitati-on was used to analyze the interaction of EZH 2 and p65 in HEK293T cells.RESULTS: The expression levels of EZH2 were significantly increased in the gastric cancer cells compared with normal gastric epithelial cells .Pharmacological inhibi-tion by DZNep or knockdown of EZH2 significantly compromised AGS and SNU-16 cell activity , cell migration and anchor-age-independent cell growth.Moreover, siRNA knockdown of EZH2 impaired NF-κB downstream targets, such as IL-8, CXCL5 and CCL20.In addition, the interaction of EZH2 and p65 was detected.CONCLUSION: EZH2 mediates the growth of gastric cancer cells through the regulation of NF-κB downstream gene expression .