The Evaluation of rs11614913 Polymorphism in MIR196A2 Gene and the Risk of Prostate Cancer in Chaharmahal and Bakhtiari Province, Iran

Document Type : Original Article (s)

Authors

1 Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

2 Associate Professor, Department of Genetics, School of Basic Sciences, Shahrekord University, Shahrekord, Iran

3 MSc Student, Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

4 Associate Professor, Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

Abstract

Background: Genetic variants affect the expression of microRNAs (miRNA) resulted in changes in the expression levels of the miRNA target genes that may lead to the increased risk of cancer. The aim of the current study was to investigate the association between the common single-nucleotide gene polymorphism T < C (rs11614913) in MIR196A2 and the risk of developing prostate cancer (PCa) in Chahar Mahal and Bakhtiari Province, Iran.Methods: In this case-control study, 99 patients were enrolled in the case group and 100 healthy controls in the control group. From all participants, 5 ml venous blood sample was collected and DNA was extracted by phenol-chloroform extraction. Specific primers were designed for rs11614913 polymorphism, and this polymorphism was genotyped using High Resolution Melt (HRM) analysis. Hardy-Weinberg equilibrium for the genotypes was tested by chi-squared test. The association between different genotypes and the risk of prostate cancer was investigated by logistic regression analysis.Findings: Among 99 patients, 68 had prostate cancer and 31 had benign prostatic hyperplasia (BPH). Logistic regression analysis showed that those cases with CC genotype had a higher risk of developing prostate cancer [Odds ratio (OR) = 1.08] than T (TT+CT) carriers. Allele frequency analysis revealed that the C allele increased the risk of developing prostate cancer and BPH 1.3 more than T allele.Conclusion: The C allele in rs11614913 polymorphism increases the risk of prostate cancer. Because this polymorphism is present in MIR196A2 gene, evaluation of expression of the miRNA gene and its target genes in patients with prostate cancer could be valuable.

Keywords


  1. Lin MC, Wang M, Chou MC, Chao CN, Fang CY, Chen PL, et al. Gene therapy for castration-resistant prostate cancer cells using JC polyomavirus-like particles packaged with a PSA promoter driven-suicide gene. Cancer Gene Ther 2019; 26(7): 208-15.
  2. Vannini I, Fanini F, Fabbri M. Emerging roles of microRNAs in cancer. Curr Opin Genet Dev 2018; 48: 128-33.
  3. Ryan BM, Robles AI, Harris CC. Genetic variation in microRNA networks: The implications for cancer research. Nat Rev Cancer 2010; 10(6): 389-402.
  4. Liu Y, He A, Liu B, Zhong Y, Liao X, Yang J, et al. rs11614913 polymorphism in miRNA-196a2 and cancer risk: An updated meta-analysis. Onco Targets Ther 2018; 11: 1121-39.
  5. Hu Z, Chen J, Tian T, Zhou X, Gu H, Xu L, et al. Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest 2008; 118(7): 2600-8.
  6. Zhao H, Xu J, Zhao D, Geng M, Ge H, Fu L, et al. Somatic mutation of the SNP rs11614913 and Its association with increased MIR 196A2 expression in breast cancer. DNA Cell Biol 2016; 35(2): 81-7.
  7. George GP, Gangwar R, Mandal RK, Sankhwar SN, Mittal RD. Genetic variation in microRNA genes and prostate cancer risk in North Indian population. Mol Biol Rep 2011; 38(3): 1609-15.
  8. Doulah A, Salehzadeh A, Mojarrad M. Association of single nucleotide polymorphisms in miR- 499 and miR-196a with susceptibility to breast cancer. Trop J Pharm Res 2018; 17(2): 319-23.
  9. Damodaran M, Paul SFD, Venkatesan V. Genetic polymorphisms in miR-146a, miR-196a2 and miR-125a genes and its association in prostate cancer. Pathol Oncol Res 2018. [Epub ahead of print].
  10. Nikolic Z, Savic PD, Vucic N, Cidilko S, Filipovic N, Cerovic S, et al. Assessment of association between genetic variants in microRNA genes hsa-miR-499, hsa-miR-196a2 and hsa-miR-27a and prostate cancer risk in Serbian population. Exp Mol Pathol 2015; 99(1): 145-50.
  11. Wang F, Ma YL, Zhang P, Yang JJ, Chen HQ, Liu ZH, et al. A genetic variant in microRNA-196a2 is associated with increased cancer risk: A meta-analysis. Mol Biol Rep 2012; 39(1): 269-75.
  12. Chu H, Wang M, Shi D, Ma L, Zhang Z, Tong N, et al. Hsa-miR-196a2 Rs11614913 polymorphism contributes to cancer susceptibility: Evidence from 15 case-control studies. PLoS One 2011; 6(3): e18108.
  13. Zhang H, Su YL, Yu H, Qian BY. Meta-analysis of the association between mir-196a-2 polymorphism and cancer susceptibility. Cancer Biol Med 2012; 9(1): 63-72.
  14. Srivastava K, Srivastava A. Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk. PLoS One 2012; 7(11): e50966.
  15. Xu W, Xu J, Liu S, Chen B, Wang X, Li Y, et al. Effects of common polymorphisms rs11614913 in miR-196a2 and rs2910164 in miR-146a on cancer susceptibility: A meta-analysis. PLoS One 2011; 6(5): e20471.
  16. He B, Pan Y, Cho WC, Xu Y, Gu L, Nie Z, et al. The association between four genetic variants in microRNAs (rs11614913, rs2910164, rs3746444, rs2292832) and cancer risk: evidence from published studies. PLoS One 2012; 7(11): e49032.
  17. Xu Y, Gu L, Pan Y, Li R, Gao T, Song G, et al. Different effects of three polymorphisms in MicroRNAs on cancer risk in Asian population: Evidence from published literatures. PLoS One 2013; 8(6): e65123.
  18. Sumanasuriya S, De BonoJ. Treatment of advanced prostate cancer-a review of current therapies and future promise. Cold Spring Harb Perspect Med 2018; 8(6): 1-13.
  19. Balistreri CR, Candore G, Lio D, Carruba G. Prostate cancer: from the pathophysiologic implications of some genetic risk factors to translation in personalized cancer treatments. Cancer Gene Ther 2014; 21(1): 2-11.