Expression Of PAX2 In Endometrial Carcinoma And Regulation Of Its DNA Methylation

Objective:To investigate the expression, methylation and the role of PAX2 in carcinogenesis of endometrial cancer, and the possible regulative mechanism of PAX2 expression.Methods:The expression of PAX2 was detected by immunohistochemistry in endometrial cancer, hyperplasia and normal tissues. And its correlation with clinical pathological characteristics was analyzed. Cell abilities of proliferation, invasion and migration were detected by CCK-8, transwell and wound healing test after PAX2 knockdown by small RNA interference. Bisulfite sequencing and MassARRAY were used to quantify the DNA methylation level of PAX2 promoter of endometrial cells and tissues. PAX2 expression and DNA methylation was measured by western blot, immunocytochemistry and bisulfite sequencing in endometrial cancer cell lines after 5-Aza-CdR treatment. Transcription factors which may bind to the fragment with differentiated methylation levels were forecasted by TF search database.Results:PAX2 was overexpressed in endometrial cancer tissues compared with hyperplasia and normal endometrium, whose expression was correlated with p53 expression. Cell proliferation and invasion was inhibited when PAX2 was knockdown, while the ability of cell migration was not changed. The methylation level of PAX2 promoter was higher than normal counterparts in both cancer tissues and cells, which was consistent with PAX2 expression. When given 5-Aza-CdR, the PAX2 protein was down-regulated along with the methylation level of PAX2 promoter. Hypermethylation of PAX2 promoter may regulate its expression through EGR family or c-Ets-1 transcription factors.Conclusion:PAX2 was involved in cell proliferation and invasion of endometrial cancer cells, and it’s overexpression in endometrial cancer may be regulated by promoter hypermethylation.