Epigenetic Regulation of Human Riboflavin Transporter 2(hRFT2) in Cervical Cancers from Uighur Women


In the present study, we studied the hypermethylation of the human riboflavin transporter 2 (hRFT2) gene andregulation of protein expression in biopsies from resected tissues from Uighur cervical squamous cell carcinoma(CSCC) patients and their neighboring normal tissues. hRFT2 gene promoter region methylation sequences weremapped in cervical cancer cell line SiHa by bisulfite-sequencing PCR and quantitative detection of methylatedDNA from 30 pairs of Uighur’s CSCCs and adjacent normal tissues by MassARRAY (Sequenom, San Diego, CA,USA) and hRFT2 protein expression was analyzed by immunohistochemistry. In SiHa, we identified 2 CG sitesmethylated from all of 12CpG sites of the hRFT2 gene. Analysis of the data from quantitative analysis of singleCpG site methylation by Sequenom MassARRAY platform showed that the methylation level between two CpGsites (CpG 2 and CpG 3) from CpG 1~12 showed significant differences between CSCC and neighboring normaltissues. However, the methylation level of whole target CpG fragments demonstrated no significant variationbetween CSCC (0.476±0.020) and neighboring normal tissues (0.401±0.019, p>0.05). There was a tendency fortranslocation the hRFT2 proteins from cytoplasm/membrane to nucleus in CSCC with increase in methylationof CpG 2 and CpG 3 in hRFT2gene promoter regions, which may relate to the genesis of CSCC. Our resultssuggested that epigenetic modifications are responsible for aberrant expression of the hRFT2 gene, and mayhelp to understand mechanisms of cervical carcinogenesis.