The Promoter Region Of MiR-146a And Its Polymorphism In Prostate Cancer Carcinogenesis

Objective:Previous studies have documented that miR-146a is associated with the biologic processes of prostate cancer(CaP). To explore whether the promoter region of miR-146a and its polymorphism (rs73318382 A>C, rs57095329 A>G, rs6864584 T>C) play any role in CaP, we analyzed the association between these polymorphisms and the risk of CaP in southeastern Chinese Han population. Moreover, the expression of miR-146a with different genotypes was tested to investigate the CaP probable carcinogenesis.Materials and Methods:The case-control study consisted of 126 CaP patients diagnosed through biopsy and 134 cancer-free controls frequency-mated with the cases by age. We conducted gene sequencing of approximately 1000bp in promoter region of miR-146a to genotype the polymorphisms and evaluated their association with CaP risk. Then the luciferase assay in different CaP cell lines (DU145 and LNCap) were designed to analysis the association between this polymorphism and the transcriptional activity of miR-146a.Results:A significantly decreased risk of prostate cancer was found for the rs57095329 AG genotype (OR=0.50; 95%CI=0.28-0.88) and rs57095329 AG/GG genotype (OR=0.49; 95%CI=0.29-0.83), compared with the AA genotype. However, no significant association was found between the polymorphism rs73318382 A>C and rs6864584 T>C) and CaP susceptibility. The luciferase assay in different CaP cell lines (DU145 and LNCap) showed an increased transcriptional activity of the rs57095329 G allele compared with the rs57095329 A allele (P<0.05).Conclusions:The polymorphism rs57095329 A>G in the miR-146a promoter region may alter the susceptibility of CaP in Chinese population, and has the potential to be used as a CaP susceptibility biomarker in the future prevention, diagnosis and treatment. More deep-going studies with large sample size in other ethnic are needed to validate these results.