Correlation Between Single Nucleotide Polymorphisms of an miRNA Binding Site in the 3'UTR of PTEN and Risk of Cervical Cancer Among the Han Chinese.

Abstract

Objective: To analyze the association between a single nucleotide polymorphism (SNP) in the 3' untranslated region (UTR) of the phosphatase and tensin homolog (PTEN) gene, that is within a microRNA (miRNA) binding site, and the risk of Chinese Han cervical cancer. Methods: A case-control study was carried out to analyze the genotype of the PTEN rs34140758 locus in 210 surgically treated, Han Chinese, cervical cancer patients and 210 healthy controls. The levels of the miRNAs hsa-miR-586 and hsa-miR-622 and the PTEN mRNA were analyzed by real-time reverse transcription-quantitative polymerase chain reaction in the cancerous and adjacent normal tissues from all cases. HeLa cells were transfected with the miRNAs, hsa-miR-586 and hsa-miR-622, to analyze their effects on PTEN gene expression. Results: After adjusting for age, body-mass index, alcohol consumption, smoking, and familial history of cancer, the PTEN rs34140758 A allele carriers were 1.47 times more likely to suffer from cervical cancer than the C allele carriers (odds ratio [OR] = 1.47, 95% confidence interval [CI]: 1.17-1.72, p = 0.001). Both hsa-miR-586 and hsa-miR-622 were highly expressed in the cancerous tissues of the cervical cancer patients, whereas PTEN expression was low. HeLa cell transfection experiments showed that hsa-miR-586 and hsa-miR-622 inhibited PTEN gene expression. The results of a dual-luciferase reporter assay showed that the PTEN gene is a target for both hsa-miR-586 and hsa-miR-622. Conclusion: The PTEN 3'UTR rs34140758 locus SNP is associated with the risk of cervical cancer in the Han Chinese population. The molecular mechanism may be that the rs34140758 SNP affects the regulation of PTEN gene expression through interaction with the hsa-miR-586 and hsa-miR-622 miRNAs.