The role of PAQR3 gene promoter hypermethylation in breast cancer and prognosis

PAQR3 is a tumor suppressor in breast cancer and its expression regulation mechanism has not been well elucidated. In this study, we found that PAQR3 expression was downregulated in breast cancer tissues, and the downregulation of PAQR3 expression was found to be significantly associated with aberrant methylation of the gene promoter. Methylation-specific PCR showed that hypermethylation of the PAQR3 gene was observed in 71.8% of the breast cancers, whereas it was found in only 28.2% of the corresponding non-tumor tissues. Moreover, we found that the PAQR3 promoter methylation status was related to lymph node metastasis (P=0.01). In addition, overexpression of PAQR3 inhibited breast cancer cell invasion and growth. Furthermore, PAQR3 expression was restored in MCF-7 cells after treatment with the demethylating agent, 5-aza-2-deoxy-cytidine, and the effect of demethylation induced invasion and proliferation suppression of MCF-7 cells. Collectively, our results suggested that the aberrant methylation of PAQR3 underlies its downregulation in breast cancer and our data indicated that epigenetic silencing of PAQR3 gene expression by promoter hypermethylation may play an important role in breast cancer.