Association of rs16917496 polymorphism at the miR-502 binding site in the SET8 3'UTR with the risk of Prostate Cancer and benign prostatic hyperplasia
Background: MicroRNAs (miRNAs) can bind to the 3'-untranslated regions (UTRs) of messenger RNAs, where they interfere with translation and thereby regulate cell differentiation, apoptosis, and tumorigenesis. Genetic polymorphisms in the 3'-UTRs targeted by miRNAs alter the strength of miRNA binding in a manner that affects the behavior of individual miRNAs. The histone methyltransferase SET8 has been reported to be a regulator of Tumor Protein 53 (TP53) methylation, a tumor suppressor gene, and regulate genomic stability. Furthermore, an association between the TP53 and Prostate Cancer has been reported in several studies. The present study aimed to evaluate whether (rs16917496) polymorphism at the miR-502 binding site in the 3' untranslated region of the histone methyltransferase SET8 is associated with the expression of this gene in Benign Prostatic Hyperplasia (BPH) and prostate cancer (PCa) patients.
Materials and Methods: We examined whether an rs16917496 polymorphism is associated with the risk of PCa and BPH in the Iranian population. This case-control study included 40 patients with pathologically confirmed PCa, 59 patients with BPH, and 45 controls. The rs16917496 polymorphism was determined using a restriction fragment length polymorphism (RFLP).
Results: We found significant association of rs16917496 in benign prostatic hyperplasia (BPH). The most frequent genotype in the control, prostate cancer, and BPH groups were TT, TC, and CC, respectively.
Conclusion: This study demonstrates that the heterozygote genotype of the SET8 polymorphism in the mir-502 gene could be considered a risk factor for the emergence of prostate cancer.
Eidelman E, Twum-Ampofo J, Ansari J, Siddiqui MM. The Metabolic Phenotype of Prostate Cancer. Frontiers in oncology. 2017;7:131.
Board PDQCGE. Genetics of Prostate Cancer (PDQ(R)): Health Professional Version. PDQ Cancer Information Summaries. Bethesda (MD): National Cancer Institute (US); 2002.
Jadvar H. Multimodal Imaging in Focal Therapy Planning and Assessment in Primary Prostate Cancer. Clinical and translational imaging. 2017;5(3):199-208.
Peng X, Guo W, Liu T, et al. Identification of miRs-143 and -145 that is associated with bone metastasis of prostate cancer and involved in the regulation of EMT. PLoS One. 2011;6(5):e20341.
Hassan O, Ahmad A, Sethi S, Sarkar FH. Recent updates on the role of microRNAs in prostate cancer. Journal of hematology & oncology. 2012;5:9.
Dai X, Fang X, Ma Y, Xianyu J. Benign Prostatic Hyperplasia and the Risk of Prostate Cancer and Bladder Cancer: A Meta-Analysis of Observational Studies. Medicine. 2016;95(18):e3493.
Diao L, Su H, Wei G, et al. Prognostic value of microRNA 502 binding site SNP in the 3'-untranslated region of the SET8 gene in patients with non-Hodgkin's lymphoma. Tumori. 2014;100(5):553-8.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281-97.
Ambros V. The functions of animal microRNAs. Nature. 2004;431(7006):350-5.
Chin LJ, Ratner E, Leng S, et al. A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk. Cancer research. 2008;68(20):8535-40.
Saetrom P, Biesinger J, Li SM, et al. A risk variant in an miR-125b binding site in BMPR1B is associated with breast cancer pathogenesis. Cancer research. 2009;69(18):7459-65.
Martinez E, Silvy F, Fina F, et al. Rs488087 single nucleotide polymorphism as predictive risk factor for pancreatic cancers. Oncotarget. 2015;6(37):39855-64.
Wu S, Wang W, Kong X, et al. Dynamic regulation of the PR-Set7 histone methyltransferase is required for normal cell cycle progression. Genes & development. Nov 15 2010;24(22):2531-2542.
Jorgensen S, Elvers I, Trelle MB, et al. The histone methyltransferase SET8 is required for S-phase progression. The Journal of cell biology. Dec 31 2007;179(7):1337-1345.
Wang C, Wu J, Zhao Y, Guo Z. miR-502 medaited histone methyltransferase SET8 expression is associated with outcome of esophageal squamous cell carcinoma. Scientific reports. 2016;6:32921.
Hou L, Li Q, Yu Y, Li M, Zhang D. SET8 induces epithelialmesenchymal transition and enhances prostate cancer cell metastasis by cooperating with ZEB1. Molecular medicine reports. 2016;13(2):1681-8.
Wang C, Guo Z, Wu C, Li Y, Kang S. A polymorphism at the miR-502 binding site in the 3' untranslated region of the SET8 gene is associated with the risk of epithelial ovarian cancer. Cancer genetics. 2012;205(7-8):373-6.
Yang S, Guo H, Wei B, et al. Association of miR-502-binding site single nucleotide polymorphism in the 3'-untranslated region of SET8 and TP53 codon 72 polymorphism with non-small cell lung cancer in Chinese population. Acta biochimica et biophysica Sinica. 2014;46(2):149-54.
Song F, Zheng H, Liu B. An miR-502-binding site single-nucleotide polymorphism in the 3'-untranslated region of the SET8 gene is associated with early age of breast cancer onset. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009;15(19):6292-6300.
Guo Z, Wu C, Wang X, Wang C, Zhang R, Shan B. A polymorphism at the miR-502 binding site in the 3'-untranslated region of the histone methyltransferase SET8 is associated with hepatocellular carcinoma outcome. Int J Cancer. 2012;131(6):1318-22.