AIMS Genetics, 2016, 3(4): 212-218. doi: 10.3934/genet.2016.4.212.

Research article

Export file:


  • RIS(for EndNote,Reference Manager,ProCite)
  • BibTex
  • Text


  • Citation Only
  • Citation and Abstract

MiR-608 rs4919510 C>G polymorphism increased the risk of bladder cancer in an Iranian population

1 Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
2 Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
3 Urology and Nephrology Research Center; Department of Urology, Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Genetic of non-communicable disease research Center, Zahedan University of Medical Sciences, Zahedan, Iran
5 Department of Human Anatomy and Cell Science, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada

MicroRNAs (miRNAs) participate in diverse biological pathways and may act as oncogenes or tumor suppressors. The single nucleotide polymorphisms (SNPs) in miRNAs potentially can alter miRNA-binding sites on target genes as well as affecting miRNAs expression. The present study aimed to evaluate the impact of miR-608 rs4919510 C>G variant on bladder cancer risk. This case-control study conducted on 233 bladder cancer patients and 252 healthy subjects. Genotyping of miR-608 rs4919510 was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our findings showed that CG as well as CG+GG genotypes significantly increased the risk of bladder cancer (OR = 1.94, 95% CI = 1.28–2.94, p = 0.002, and OR = 1.90, 95% CI = 1.26–2.86, p = 0.002, respectively) compared to CC genotype. The G allele significantly increased the risk of bladder cancer compared to C allele (OR = 1.69, 95% CI = 1.17–2.45, p = 0.005). Our findings proposed that miR-608 polymorphism might be associated with increased risk of bladder cancer in a sample of Iranian population. Further large-scale studies with different ethnicities are needed to verify our findings
  Article Metrics

Keywords miR-608; bladder cancer; polymorphism

Citation: Mohammad Hashemi, Fatemeh Bizhani, Hiva Danesh, Behzad Narouie, Mehdi Sotoudeh, Mohammad Hadi Radfar, Mehdi Honarkar Ramezani, Gholamreza Bahari, Mohsen Taheri, Saeid Ghavami. MiR-608 rs4919510 C>G polymorphism increased the risk of bladder cancer in an Iranian population. AIMS Genetics, 2016, 3(4): 212-218. doi: 10.3934/genet.2016.4.212


  • 1. Torre LA, Bray F, Siegel RL, et al. (2015) Global cancer statistics, 2012. CA Cancer J Clin 65: 87-108.    
  • 2. Antoni S, Ferlay J, Soerjomataram I, et al. (2016) Bladder Cancer Incidence and Mortality: A Global Overview and Recent Trends. Eur Urol.
  • 3. Cancer Genome Atlas Research N (2014) Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 507: 315-322.    
  • 4. Shiels MS, Gibson T, Sampson J, et al. (2014) Cigarette smoking prior to first cancer and risk of second smoking-associated cancers among survivors of bladder, kidney, head and neck, and stage I lung cancers. J Clin Oncol 32: 3989-3995.    
  • 5. Vermeulen SH, Hanum N, Grotenhuis AJ, et al. (2015) Recurrent urinary tract infection and risk of bladder cancer in the Nijmegen bladder cancer study. Br J Cancer 112: 594-600.    
  • 6. Burger M, Catto JW, Dalbagni G, et al. (2013) Epidemiology and risk factors of urothelial bladder cancer. Eur Urol 63: 234-241.    
  • 7. Giedl J, Rogler A, Wild A, et al. (2016) TERT Core Promotor Mutations in Early-Onset Bladder Cancer. J Cancer 7: 915-920.    
  • 8. Sankhwar M, Sankhwar SN, Bansal SK, et al. (2016) Polymorphisms in the XPC gene affect urinary bladder cancer risk: a case-control study, meta-analyses and trial sequential analyses. Sci Rep 6: 27018.    
  • 9. Hua Q, Lv X, Gu X, et al. (2016) Genetic variants in lncRNA H19 are associated with the risk of bladder cancer in a Chinese population. Mutagenesis: gew018
  • 10. Aben KK, Witjes JA, Schoenberg MP, et al. (2002) Familial aggregation of urothelial cell carcinoma. Int J Cancer 98: 274-278.    
  • 11. He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5: 522-531.    
  • 12. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116: 281-297.    
  • 13. Lee Y, Kim M, Han J, et al. (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23: 4051-4060.    
  • 14. Ryan BM, Robles AI, Harris CC (2010) Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer 10: 389-402.    
  • 15. Landi D, Gemignani F, Barale R, et al. (2008) A catalog of polymorphisms falling in microRNA-binding regions of cancer genes. DNA Cell Biol 27: 35-43.    
  • 16. Wei WJ, Wang YL, Li DS, et al. (2015) Association study of single nucleotide polymorphisms in mature microRNAs and the risk of thyroid tumor in a Chinese population. Endocrine 49: 436-444.    
  • 17. Jiao L, Zhang J, Dong Y, et al. (2014) Association between miR-125a rs12976445 and survival in breast cancer patients. Am J Transl Res 6: 869-875.
  • 18. Kupcinskas J, Bruzaite I, Juzenas S, et al. (2014) Lack of association between miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 gene polymorphisms and colorectal cancer. Sci Rep 4: 5993.
  • 19. Lin M, Gu J, Eng C, et al. (2012) Genetic polymorphisms in MicroRNA-related genes as predictors of clinical outcomes in colorectal adenocarcinoma patients. Clin Cancer Res 18: 3982-3991.    
  • 20. Ryan BM, McClary AC, Valeri N, et al. (2012) rs4919510 in hsa-mir-608 is associated with outcome but not risk of colorectal cancer. PLoS One 7: e36306.    
  • 21. Wang R, Zhang J, Ma Y, et al. (2014) Association study of miR149 rs2292832 and miR608 rs4919510 and the risk of hepatocellular carcinoma in a largescale population. Mol Med Rep 10: 2736-2744.
  • 22. Zhang P, Wang J, Lu T, et al. (2015) miR-449b rs10061133 and miR-4293 rs12220909 polymorphisms are associated with decreased esophageal squamous cell carcinoma in a Chinese population. Tumour Biol 36: 8789-8795.    
  • 23. Morales S, Gulppi F, Gonzalez-Hormazabal P, et al. (2016) Association of single nucleotide polymorphisms in Pre-miR-27a, Pre-miR-196a2, Pre-miR-423, miR-608 and Pre-miR-618 with breast cancer susceptibility in a South American population. BMC Genet 17: 109.
  • 24. Ma XP, Yu G, Chen X, et al. (2016) MiR-608 rs4919510 is associated with prognosis of hepatocellular carcinoma. Tumour Biol 2016: 1-12.
  • 25. Sclafani F, Chau I, Cunningham D, et al. (2016) Sequence Variation in Mature MicroRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients. Carcinogenesis: bgw073.
  • 26. Jiang J, Jia ZF, Cao DH, et al. (2016) Association of the miR-146a rs2910164 polymorphism with gastric cancer susceptibility and prognosis. Future Oncol 0.
  • 27. Yang PW, Huang YC, Hsieh CY, et al. (2014) Association of miRNA-related Genetic Polymorphisms and Prognosis in Patients with Esophageal Squamous Cell Carcinoma. Ann Surg Oncol 21: 601-609.    
  • 28. Hashemi M, Sanaei S, Rezaei M, et al. (2016) miR-608 rs4919510 C>G polymorphism decreased the risk of breast cancer in an Iranian subpopulation. Exp Oncol 38: 57-59.
  • 29. Qiu F, Yang L, Zhang L, et al. (2015) Polymorphism in mature microRNA-608 sequence is associated with an increased risk of nasopharyngeal carcinoma. Gene 565: 180-186.    
  • 30. Huang AJ, Yu KD, Li J, et al. (2012) Polymorphism rs4919510:C>G in mature sequence of human microRNA-608 contributes to the risk of HER2-positive breast cancer but not other subtypes. PLoS One 7: e35252.    
  • 31. Dai ZM, Kang HF, Zhang WG, et al. (2016) The Associations of Single Nucleotide Polymorphisms in miR196a2, miR-499, and miR-608 With Breast Cancer Susceptibility: A STROBE-Compliant Observational Study. Medicine (Baltimore) 95: e2826.    
  • 32. Yin Z, Cui Z, Guan P, et al. (2015) Interaction between Polymorphisms in Pre-MiRNA Genes and Cooking Oil Fume Exposure on the Risk of Lung Cancer in Chinese Non-Smoking Female Population. PLoS One 10: e0128572.    
  • 33. Yin Z, Cui Z, Ren Y, et al. (2016) Association between polymorphisms in pre-miRNA genes and risk of lung cancer in a Chinese non-smoking female population. Lung Cancer 94: 15-21.    
  • 34. Kupcinskas J, Wex T, Link A, et al. (2014) Gene polymorphisms of micrornas in Helicobacter pylori-induced high risk atrophic gastritis and gastric cancer. PLoS One 9: e87467.    
  • 35. Wang K, Liang Q, Wei L, et al. (2016) MicroRNA-608 acts as a prognostic marker and inhibits the cell proliferation in hepatocellular carcinoma by macrophage migration inhibitory factor. Tumour Biol 37: 3823-3830.    
  • 36. Xing J, Wan S, Zhou F, et al. (2012) Genetic polymorphisms in pre-microRNA genes as prognostic markers of colorectal cancer. Cancer Epidemiol Biomarkers Prev 21: 217-227.    
  • 37. Pardini B, Rosa F, Naccarati A, et al. (2015) Polymorphisms in microRNA genes as predictors of clinical outcomes in colorectal cancer patients. Carcinogenesis 36: 82-86.    
  • 38. Liu H, Zhou Y, Liu Q, et al. (2016) Association of miR-608 rs4919510 polymorphism and cancer risk: a meta-analysis based on 13,664 subjects. Oncotarget.
  • 39. Rah H, Kim HS, Cha SH, et al. (2015) Association of breast cancer-related microRNA polymorphisms with idiopathic primary ovarian insufficiency. Menopause 22: 437-443.    
  • 40. Li D, Zhu G, Di H, et al. (2016) Associations between genetic variants located in mature microRNAs and risk of lung cancer. Oncotarget.
  • 41. Zhang Y, Schiff D, Park D, et al. (2014) MicroRNA-608 and microRNA-34a regulate chordoma malignancy by targeting EGFR, Bcl-xL and MET. PLoS One 9: e91546.    
  • 42. Hezaveh K, Kloetgen A, Bernhart SH, et al. (2016) Alterations of miRNAs and miRNA-regulated mRNA expression in GC B cell lymphomas determined by integrative sequencing analysis. Haematologica.
  • 43. Marzec-Kotarska B, Cybulski M, Kotarski JC, et al. (2016) Molecular bases of aberrant miR-182 expression in ovarian cancer. Genes Chromosomes Cancer 55: 877-889.    


This article has been cited by

  • 1. Norahayu Othman, Noor Hasima Nagoor, miR-608 regulates apoptosis in human lung adenocarcinoma via regulation of AKT2, International Journal of Oncology, 2017, 51, 6, 1757, 10.3892/ijo.2017.4174
  • 2. Mohammad Hashemi, Gholamreza Bahari, Fatemeh Bizhani, Hiva Danesh, Shamim Sarhadi, Seyed Amir Mohsen Ziaee, Abbas Basiri, Behzad Narouie, Mohsen Taheri, Saeid Ghavami, Evaluation of 4-bp insertion/deletion polymorphism within the 3′UTR of SGSM3 in bladder cancer using mismatch PCR-RFLP method: A preliminary report, Journal of Cellular Biochemistry, 2018, 10.1002/jcb.26764

Reader Comments

your name: *   your email: *  

Copyright Info: 2016, Mohammad Hashemi, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (

Download full text in PDF

Export Citation

Copyright © AIMS Press All Rights Reserved