Methylation of RUNX3 gene in epithelial ovarian carcinoma

Abstract

Objective To access the role of methylated RUNX3 ggene in the carcinogenesis an progression of ovarian carcinoma.Methods Sample of 32 epithelial ovarian carcinoma tissues,32 para-carcinoma tissues,36 benign epithelial tumors and 10 normal ovarian tissues and 2 cell lines(3A0 and SKOV3),were collected and subject to methylation-specific PCR(MSP).Promoter methylation status of RUNX3 in two tumor cell lines were analyzed before and after 5-aza-2'deoxycytidine treatment.In addition. mRNA expression of RUNX3 were investigated by quantitative reverse transcription-PCR Results CpG island methylation of RUNX3 was observed in 53.1%(17 of 32)of epithelial ovarian cancer,and 37.5% (12 of 32)in corresponding noncancerous tissues,16.7% in benign epithelial tumors(6 of 36),and all celllines,but not in normal control tissues.The prevalence of RUNX3 gene CpG methylation in malignantwas significantly higher than those in benign and normal tissues(X2=10.060,X2=8.925,P<0.05). Nineteen percent(6 of 32)of ovarian epithelial carcinoma expressed RUNX3 mRNA,while its expression Was present in 28% (9 of 32)corresponding noncancerous tissues and 72% (26 of 36)of benign ovarian tumor and 80% (8 of 10)of normal ovarian tissues.The RUNX3 promoter methylation was found in all cell lines tested.The ratio of expression of RUNX3 mRNA in ovarian epithelial carcinoma was significantly lower than those of normal and benign tumors(X2=19.443,X2=12.862,P<0.05).After 5-aza-2'deoxycytidine treatment,methylation was partially or completely reversed,and its mRNA expression was increased.The relationship between gene expression and promoter methylation was reversely correlated.Conclusions Our results suggest that promoter hypermethylation of RUNX3 genes is common in ovarian cancer. Therefore, hypermethylation of RUNX3 genes may be involved in the carcinogenesis of ovarian cancer and may serve as an early diagnostic marker for ovarian cancer. The close correlation between RUNX3 methylation of its mRNA suggests that methylation which can be reversed.Thus,it provides a new way for therapy of ovarian Cancer. Key words: Ovarian neoplasms; DNA binding proteins; Transcription factors; Promoter regions(genetic)DNA methelation