Association Between Promoter Methylation and Gene Expression of and in HPV-infected Cervical Cancer Cells
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Overexpression of the gene of human papillomavirus (HPV) type 16 is one of the primary causes of cervical cancer. The E7 protein can bind with DNA methyltransferase I and induce methylation of tumor suppressor genes, such as cyclin-A1 (), leading to suppression of their expression, and thus, cancer progression. In the present study, the confirmation of methylation-related expression of chorionic gonadotropin subunit 3 () and nucleolar protein 56 () genes in 5-Azacytidine (5'-aza)-treated HPV16-positive SiHa and HPV16-negative C33A cell lines was shown. Using methylation-specific-PCR and quantitative PCR, the results showed that and methylation significantly decreased as the 5'-aza concentration was increased, and this was inversely associated with their expression. Moreover, overexpression of E7 contributed to the augmentation of and methylation levels in C33A cells, resulting in a decrease in their expression. This study extends on previous observations of HPV16 oncogenic function in terms of methylation-repressing expression in more genes, which may be wholly applied to gene therapy in cervical cancer prevention.
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