Two prostate cancer‑associated polymorphisms in the 3'UTR of IGF1R influences prostate cancer susceptibility by affecting miRNA binding.

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.