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4 752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 ＜0.05).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IGF1R 3'UTR的结合更稳定,miR-141与IGF1R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:IGF1R 3'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.%Objective:To study the relationship of IGF1R 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 predicted 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.Results:miR-141 was predicted to be binding to rs3743249 by analysis of database.IGF1R mRNA was upregulated significantly in PCa tissues in TCGA datasets (P ＜0.05).MiR-141 showed significant upregulation in PCa tissues in TCGA and GEO datasets (GSE23022 and GSE36803) compared with adjacent tissues of paired(P ＜0.05).Dual luciferase reporter assay indicated that miR-141 showed a stronger binding affinity with rs3743249 in the 3'UTR of IGF1R,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.
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