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骨形态发生蛋白受体型 IB 基因中 miR-125b 结合位点多态性与中国前列腺癌风险。

A miR-125b binding site polymorphism in bone morphogenetic protein membrane receptor type IB gene and prostate cancer risk in China.

机构信息

Department of Urology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.

出版信息

Mol Biol Rep. 2012 Jan;39(1):369-73. doi: 10.1007/s11033-011-0747-9. Epub 2011 May 10.

Abstract

Recently, a C>T polymorphism (rs1434536) in a miR-125b binding site in the 3' untranslated region (3'UTR) of bone morphogenetic protein membrane receptor type IB gene (BMPR1B) has been found to contribute to cancer susceptibility. To investigate whether it plays an important role in the development of prostate cancer in southern Chinese Han population, we performed a case-control study. 247 prostate cancer and 278 control subjects were included in the cancer association study and dual-luciferase reporter assay was used to test the binding ability of miR-125b to BMPR1B-C or -T vectors. The effect of CT/TT genotype on prostate cancer risk was found to be significant for localized disease (OR=1.60, 95% CI=1.01-2.53, P=0.044) and among subgroups of aged>70 years (OR=1.90, 95% CI=1.15-3.15, P=0.015) compared with CC genotype. Moreover, C-allele gave a reduced luciferase activity relative to T-allele in dual-luciferase reporter assay. Our findings show that rs1434536 in the 3'UTR of BMPR1B gene affects the binding ability of miR-125b to BMPR1B mRNA and contributes to the genetic predisposition to localized prostate cancer and patients aged>70 years.

摘要

最近,在骨形态发生蛋白受体型 IB 基因(BMPR1B)的 3'非翻译区(3'UTR)中 miR-125b 结合位点的 C>T 多态性(rs1434536)被发现与癌症易感性有关。为了研究其是否在南方汉族人群前列腺癌的发生发展中起重要作用,我们进行了病例对照研究。247 例前列腺癌患者和 278 例对照纳入癌症关联研究,采用双荧光素酶报告基因检测 miR-125b 与 BMPR1B-C 或 -T 载体的结合能力。结果发现,CT/TT 基因型与局限性疾病(OR=1.60,95%CI=1.01-2.53,P=0.044)和>70 岁亚组(OR=1.90,95%CI=1.15-3.15,P=0.015)的前列腺癌风险显著相关,而 CC 基因型则无显著相关性。此外,双荧光素酶报告基因检测显示,与 T 等位基因相比,C 等位基因的荧光素酶活性降低。我们的研究结果表明,BMPR1B 基因 3'UTR 中的 rs1434536 影响 miR-125b 与 BMPR1B mRNA 的结合能力,并导致局部前列腺癌和>70 岁患者的遗传易感性。

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