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

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.