Association of promoter methylation of ERp57 gene with the pathogenesis of cervical lesions in Uighur women

Abstract

To investigate the relationship and significance between endoplasmic reticulum protein 57 (ERp57) gene promoter region methylation with the pathogenesis of cervical lesions in Uighur women. The special software was used to design specific primers of CpG island fragments of ERp57 gene promoter and bisulfite-modified SiHa cancer cell DNA for PCR amplification, cloning and sequencing the target fragments to obtain relevant information of CpG methylation in the gene base sequencs. Seventy-eight fresh tissues of CIN, CSCC and normal control were collected, and the methylation level of ERp57 gene promoter regions in different cervical lesions were identified using Sequenom MassARRAY(DNA) technology. ERp57 gene corresponding target fragment contained the 18 CpG sites. All of the CpG sites methylation occurred in SiHa cervical cancer cell genomic DNA. The analysis of the data resulted from the quantitative analysis of single CpG site methylation by Sequenom MassARRAY platform showed that the methylation level between three CpG sites (CpG_1, CpG_5 and CpG_7) from CpG_1, CpG_2, CpG_3.4, CpG_5, CpG_6, CpG_7, CpG_8 and CpG_ 9 had significant differences in the CSCC, CIN or control groups. Although the global methylation level of the ERp57 gene promoter is higher in CSCC than that in CIN and normal control tissues in Uighur women, hypermethylation occurs only in certain CpG islands and sites. This indicates that the regulation of expression by DNA methylation is not CpG island-specific, but varies for individual CpG sites, and may explain to a certain extent the epigenetic mechanisms regulated by Erp57 gene expression.