Abstract: Objective To investigate the effect of DNA methyltransferase 1 (DNMT1) on the growth and metastasis of cervical cancer (CC) by regulating the expression of sex determining region Y-box 1 (SOX1). Methods Bisulfite quantitative PCR was used to determine the SOX1 methylation level in CC tissues and cells, CC adjacent tissues and normal cervical cells. Western blot assay was used to detect the protein expression levels of DNMT1 and SOX1. HeLa229 and SW756 cells were divided into the DNMT1-NC group, the DNMT1-siRNA group and the blank group. Bisulfite quantitative PCR was used to determine the SOX1 methylation ratio. Western blot assay was used to detect the DNMT1, SOX1, c-Myc, Cyclin D1 and β-catenin protein expression. The cell cloning and nude mouse tumor formation experiments were used to measure cell proliferation, and Transwell experiment was used to measure cell migration and invasion. Results The expression level of DNMT1 and the methylation ratio of SOX1 were higher in CC tissues than those in adjacent tissues, while the expression of SOX1 protein was significantly lower (P＜0.05). The expression level of DNMT1 and the methylation ratio of SOX1 in cervical cancer HeLa229, ME-180, SiHa, SW756 cells were significantly higher than those in cervical epithelial Ect1/E6E7 cells, while the expression of SOX1 protein was significantly lower (P＜0.05). Compared with the blank group and the DNMT1-NC group, the numbers of in vitro clone formation, migration and invasion of HeLa229 and SW756 cells decreased in the DNMT1-siRNA group, and the tumor mass was reduced in nude mice. The protein expression and SOX1 methylation ratio of DNMT1, c-Myc, Cyclin D1, and nuclear/plasma β -catenin decreased, SOX1 protein expression increased (P＜0.05). Conclusion DNMT1 is highly expressed in CC tissues and cells, and it may promote the growth and metastasis of CC by maintaining SOX1 promoter hypermethylation and inhibiting the protein expression.

Key words: uterine cervical neoplasms, cell proliferation, cell movement, methyltransferases, sex-determining region Y protein, cell invasion, DNA methyltransferase 1, sex determining region Y-box 1