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Polymorphism in the Promoter Region of microRNA-143 Gene and Genetic Susceptibility of Prostate Cancer

Author: TangJiaLin
Tutor: ZhangZhengDong
School: Nanjing Medical University
Course: Occupational and Environmental Health
Keywords: miR-143 Promoter region Polymorphism Prostate cancer Genetic susceptibility Molecular Epidemiology
CLC: R737.25
Type: Master's thesis
Year: 2011
Downloads: 111
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Abstract


Objective: micro RNA (microRNAs, miRNAs) is a newly discovered class of endogenous non-coding RNA, is generally 18 ~ 22 nucleotides, can be degraded or inhibition of a target gene mRNA and play the role of tumor suppressor gene or an oncogene-like . Genetic variation, such as single nucleotide polymorphisms (single nucleotide polymorphisms, SNPs) may change the formation and expression of miRNA, which may affect tumor development and progression. microRNA-143 (miR-143) play in the development and progression of prostate cancer, bladder cancer, leukemia, colorectal cancer and other tumors, the tumor inhibition. We hypothesized that the promoter region of miR-143 rs4705342 T gt; C polymorphism and genetic susceptibility of Chinese Han population prostate cancer association. Methods: Based on the molecular epidemiology of hospital case - control study, including 608 cases diagnosed by pathological cases of prostate cancer and 709 patients not suffering from cancer and age of cases were frequency matched healthy control subjects. By TaqMan genotyping analysis of the rs4705342 T GT of the promoter region of miR-143; C polymorphism and prostate cancer risk associated. Bioinformatics software to predict the RS 4,705,342 T GT; C sites may exist transcriptional binding factor and a luciferase reporter gene transient transfection experiments to explore the rs4705342 T GT; C gene transcriptional activity of miR-143. Results: miR-143 promoter region rs4705342 T GT; the C polymorphic loci and prostate cancer genetic susceptibility significant association. Compared to carry rs4705342 TT genotype carrying the rs4705342 TC or CC genotype of developing prostate cancer risk was reduced by 29% and 42% (TC vs. TT: adjust OR = 0.71; 95% CI = 0.56-0.89; CC vs. TT: adjust OR = 0.58; 95% CI = 0.39-0.85). significant dose - response relationship (Ptrend = 0.001) between rs4705342 C allele was associated with lower risk of prostate cancer. Stratified analysis found that the protective effect of the age ≤ 70 years of age (P = 0.005, adjust OR = 0.62, 95% CI = 0.45-0.87), smokers (P = 0.001, adjust OR = 0.59, 95% CI = 0.43- 0.79) and no family history of cancer (P = 0.001, adjust OR = 0.63, 95% CI = 0.50-0.81) population more pronounced. Luciferase reporter gene in different prostate cancer cell lines (DU145 and PC3) results suggest that, compared with the reporter gene carrying the rs4705342 T allele, carrying the rs4705342 C allele the report gene transcription activity was significantly increased (P = 0.001). Conclusion: miR-143 promoter region rs4705342 T gt; the C polymorphic loci may affect the genetic susceptibility of the Chinese population of prostate cancer, as a potential prostate cancer genetic susceptibility markers used in the prevention, diagnosis and treatment. The study findings need to be multi-center, multi-ethnic, the study of the large sample size verification.

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CLC: > Medicine, health > Oncology > Genitourinary tumors > Male genitalia tumors > Prostate cancer
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