The SNP rs4846048 of MTHFR enhances the cervical cancer risk through association with miR-522: A preliminary report

Abstract

Background: The present research was designed to explore the association between single nucleotide polymorphisms (SNPs) at the 3′-untranslated region (3′-UTR) of methylenetetrahydrofolate reductase (MTHFR) and the risk of cervical cancer (CC). Methods: From May 2015 to October 2016, a total of 197 patients (diagnosed with CC and precancerous lesions, and underwent surgical treatments) were enrolled in the study. Meanwhile, a total of 80 healthy cases were used as the controls. PCR-DNA analysis was used to explore the genotype of the SNPs (rs4846048 and rs55763075) of the MTHFR 3′-UTR as well as the association between allelic frequencies and the CC risk. Then, the role of rs4846048 SNPs in the association of microRNA-522 (miR-522) and MTHFR was evaluated through luciferase reporter assay. Meanwhile, the modulatory influence of miR-522 on cell apoptosis and viability of Hela cells was also detected by flow cytometry and MTT assay. Results: The rs4846048 AG and G allele frequencies were significantly higher in CC subgroup compared with the control group. Methylenetetrahydrofolate reductase rs4846048 A/G alleles contributed to miR-522 binding, and miR-522 negatively modulated the expressions of MTHFR. Furthermore, miR-522 overexpression increased cell viability but decreased apoptotic cells in Hela cells. Conclusion: The preliminary report revealed that the SNP rs4846048 of MTHFR enhanced the risk of CC through association with miR-522, which further regulated cell viability and apoptosis in Hela cells.