Association between promoter methylation and gene expression of CGB3 and NOP56 in HPV-infected cervical cancer cells

Overexpression of the E7 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 (CCNA1), 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 (CGB3) and nucleolar protein 56 (NOP56) 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 CGB3 and NOP56 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 CGB3 and NOP56 methylation levels in C33A cells, resulting in a decrease in their expression. This study extends on previous observations of E7 HPV16 oncogenic function in terms of methylation-repressing expression in more genes, which may be wholly applied to gene therapy in cervical cancer prevention.