中文摘要：

目的：探讨位于胰岛素样生长因子1受体（IGF1R）基因3’非翻译区（uTR）的前列腺癌（PCa）相关的多态性位点rs3743249与靶microRNA（miRNA）结合位点的改变对PCa发展风险的影响。方法：用miRbase预测与rs3743249结合相关的靶miRNA，分析从癌症基因组图谱（TCGA）数据库下载IGF1R基因mRNA和靶miRNA的表达数据，同时筛选符合纳入标准的GEO数据集，对基于TCGA数据分析的靶miRNA结果进行验证，采用双荧光素酶报告基因技术对转染后的人胚肾细胞（HEK293T）在体外检测rs3743249的不同等位位点对靶miRNA结合的影响。结果：rs3743249位于IGF1R的3’UTR第4752个碱基，与其结合相关的靶miRNA为miR-141。用TCGA数据分析IGF1R基因显示，IGF1R在PCa组织显著上调（P〈0．05）；与配对的癌旁组织相比，miR-141在3套公共数据（TCGA、GSE23022和GSE36803）的PCa组织样本中均显著上调（均P〈O．05）。双荧光素酶报告基因的检测结果显示，miR-141与含rs3743249等位位点为G的IGF1R3’UTR的结合更稳定，miR-141与IGFIR基因的结合起到稳定IGF1R基因表达的作用，而不是抑制作用。结论：IGF1R3’UTR多态性位点rs3743249等位位点G在促进PCa发展上风险性更大，遗传突变影响PCa的发展风险。

英文摘要：

Objective： To study the relationship of IGFIR 3＇ untranslated region （UTR） polymorphism rs3743249 caused variation of binding affinity to miR-141 and the risk of prostate cancer （PCa）. Methods： MiRNAs which could bind to rs3743249 were predicted by miRbase. Expression of IGF1R mRNA and pre- dicted targeted miRNAs were both analyzed from the Cancer Genome Atlas （TCGA） and GEO datasets met inclusion criteria. PCa-associated miRNAs were selected and the binding affinity to alleles of rs3743249 were validated by dual luciferase reporter assay in human embryonic kidney cell （HEK293T） in vitro. Re- sults： miR-141 was predicted to be binding to rs3743249 by analysis of database. IGF1R mRNA was upreg- ulated significantly in PCa tissues in TCGA datasets （ P d0.05）. MiR-141 showed significant upregulation in PCa tissues in TCGA and GEO datasets （GSE23022 and GSE36803） compared with adjacent tissues of paired（ P d0.05）. Dual luciferase reporter assay indicated that miR-141 showed a stronger binding affinity with rs3743249 in the 3＇UTR of IGFIR, suggesting that miR-141 played a stabilizing role, rather than an inhibitory role. Conclusion： Polymorphism rs3743249 with G allele inside IGF1R 3＇ UTR shows a greater risk in the progression of PCa.