Life Sciences Institute, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Oncol Rep. 2019 Jan;41(1):512-524. doi: 10.3892/or.2018.6810. Epub 2018 Oct 22.
Prostate cancer (PCa) is a common malignant cancer in men worldwide. Numerous genetic variations have been associated with PCa, but their biological function remains unclear. Single nucleotide polymorphisms (SNPs) inside 3' untranslated region (UTR) affect gene expression, with one essential mechanism being regulation by micro (mi)RNAs. Based on data from genome‑wide association study of the Consortium for Chinese Consortium for Prostate Cancer Genetics, rs1815009 and rs2684788 inside 3'UTR of insulin‑like growth factor 1 receptor (IGF1R) presented significant genotype distribution between PCa and control samples. In the current study, targeting miRNAs were predicted using TargetScan and miRanda. The prediction was confirmed using a thermodynamic model for miRNA‑target interaction and luciferase reporter assays for miRNA binding inside IGF1R 3'UTR. Furthermore, data from public databases and miRNA overexpression further supported miRNAs function. The results suggested that miR‑133a and miR‑133b may bind near rs1815009, and miR‑455 near rs2684788, within IGF1R 3'UTR. Compared with normal tissues, miR‑133a, miR‑133b and miR‑455 exhibited significantly lower expression in PCa tissues in the public datasets analyzed. The results of the present study revealed an association between rs1815009, rs2684788 and PCa risk, which involves altered miRNA regulation and contributes to cancer susceptibility.
前列腺癌（PCa）是全球男性中常见的恶性肿瘤。许多遗传变异与 PCa 相关，但它们的生物学功能仍不清楚。3'非翻译区（UTR）内的单核苷酸多态性（SNPs）影响基因表达，其中一个重要机制是受 micro（mi）RNAs 的调节。基于中国前列腺癌遗传学联盟全基因组关联研究的数据，胰岛素样生长因子 1 受体（IGF1R）3'UTR 内的 rs1815009 和 rs2684788 与 PCa 和对照样本之间的基因型分布存在显著差异。在本研究中，使用 TargetScan 和 miRanda 预测靶向 miRNA。使用 miRNA 与靶标相互作用的热力学模型和 IGF1R 3'UTR 内 miRNA 结合的荧光素酶报告基因检测来验证预测。此外，公共数据库和 miRNA 过表达的数据进一步支持了 miRNA 的功能。结果表明，miR-133a 和 miR-133b 可能在 rs1815009 附近结合，miR-455 可能在 rs2684788 附近结合 IGF1R 3'UTR。与正常组织相比，在分析的公共数据集的 PCa 组织中，miR-133a、miR-133b 和 miR-455 的表达明显较低。本研究的结果揭示了 rs1815009、rs2684788 与 PCa 风险之间的关联，该关联涉及改变的 miRNA 调节，并导致癌症易感性。
