Polymorphism In The Promoter Region Of MicroRNA-143 Gene And Genetic Susceptibility Of Prostate Cancer

Objective: microRNAs (miRNAs) are a newly identified large class of non-coding endogenous 18~22-nucleotide RNAs that can function as tumor suppressors or oncogenes by targeting mRNA for cleavage or translational repression. Genetic variation such as single nucleotide polymorphisms (SNPs) of miRNAs might alter mature miRNA processing and expression and then be implicated in carcinogenesis or tumor progression. We hypothesized that the rs4705342 T>C polymorphism in microRNA-143 (miR-143) promoter region is associated with risk of prostate cancer (PCa) in Chinese population.Methods: The hospital-based case-control study consisted of 608 prostate cancer patients diagnosed through needle biopsy and 709 cancer-free controls frequency-mated with the cases by age. We genotyped the rs4705342 T>C polymorphism by using TaqMan method and evaluated its association with prostate cancer risk. We predicted the potential transcription factors for this genetic variant. Then the transient transfection and luciferase assay were designed to analysis the association between this polymorphism and the transcriptional activity of miR-143. Results: A significantly decreased risk of prostate cancer was found for the rs4705342 TC genotype (ajusted OR = 0.71; 95%CI = 0.56-0.89) and rs4705342 CC genotype (ajusted OR = 0.58; 95%CI = 0.39-0.85), compared with the TT genotype. The C allele was associated with the decreased risk of prostate cancer in a dose-response manner (Ptrend = 0.001). In stratified analyses, the protective effect was more dominant in≤70 years subjects (P = 0.005, adjusted OR = 0.62, 95%CI = 0.45-0.87), smokers (P = 0.001, adjusted OR = 0.59, 95%CI = 0.43-0.79) and men without family history of cancers (P = 0.001, adjusted OR = 0.63, 95%CI = 0.50-0.81). The luciferase assay in different prostate cancer cell lines (DU145 and PC3) showed an increased transcriptional activity of the rs4705342 C allele, compared with the rs4705342 T allele (P = 0.001).Conclusions: The polymorphism rs4705342 T>C in the miR-143 promoter region may alter the susceptibility of prostate cancer in Chinese population, and could be used as a potential prostate cancer susceptibility biomarker in the future prevention, diagnosis and treatment. More deepgoing studies with large sample size in other ethnic are wanted to validate these results.