Identification of differentially-expressed genes by DNA methylation in cervical cancer.

To identify novel cervical cancer-related genes that are regulated by DNA methylation, integrated analyses of genome-wide DNA methylation and RNA expression profiles were performed using the normal and tumor regions of tissues from four patients; two with cervical cancer and two with pre-invasive cancer. The present study identified 19 novel cervical cancer-related genes showing differential RNA expression by DNA methylation. A number of the identified genes were novel cervical cancer-related genes and their differential expression was confirmed in a publicly available database. Among the candidate genes, the epigenetic regulation and expression of three genes, CAMK2N1 , ALDH1A3 and PPP1R3C , was validated in HeLa cells treated with a demethylating reagent using methylation-specific polymerase chain reaction (PCR) and quantitative PCR, respectively. From these results, the expression of the CAMK2N1 , ALDH1A3 and PPP1R3C genes are were shown to be suppressed in cervical cancers by DNA methylation. These genes may be involved in the progression or initiation of cervical cancer.