Journal of Genetics

, Volume 97, Issue 5, pp 1307–1313 | Cite as

Association of a potential functional mir-520f rs75598818 G > A polymorphism with breast cancer

  • Marzieh Meshkat
  • Hamzeh Mesrian Tanha
  • Kamran GhaediEmail author
  • Mahboobeh Meshkat
Research Article


Some of the single-nucleotide polymorphisms in miRNA genes have been studied to date to find their association with the risk of breast cancer (BC). However, no study has been conducted to investigate the association of the mir-520f rs75598818 \(\hbox {G}\,{>}\,\hbox {A}\) in BC. In the present study, rs75598818 association with BC in an Iranian population has been investigated, and an in silico analysis was performed to predict the function of rs75598818 polymorphism in BC. The rs75598818 was genotyped in 129 BC patients and 144 healthy women, using the PCR-RFLP method. The frequency of alleles and genotypes were considered to find the associations between rs75598818 alleles/genotypes, and BC risk and pathological characteristics of the patients. Statistical analysis showed that the rs75598818 GA genotype was significantly associated with BC (GA versus GG, \(\hbox {OR}\,{=}\,0.50\), 95% CI: 0.25–0.98, \(P\,{=}\,0.041\)), high-stage BC (stage III/IV versus I/II, GA versus GG, \(\hbox {OR}\,{=}\,0.27\), 95% CI: 0.09–0.81, \(P\,{=}\,0.015\)), and HER-2 positive status (GA versus GG, \(\hbox {OR}\,{=}\,19.00\), 95% CI: 4.64–77.82, \(P\,{<}\,0.001\)). Notably, the rs75598818 GA genotype has a negative association pattern since it reduces the risk of BC and high stage BC. Conversely, it increases the risk of HER-2 positivity. Computational results suggested that the rs75598818 polymorphism affects the stability of mir-520f stem-loop and as a result miR-520f-3p production that is a potential tumour suppressor. A contribution of the mir-520f rs75598818 polymorphism to BC had been unexplored before. In the present study, we performed an association study and a bioinformatics approach to evaluate this polymorphism in BC. However, further functional experiments and large-scale association studies with various ethnicities are required to elaborate our findings.


advanced breast cancer bioinformatics functional SNP HER-2 miRNA 


  1. Anderson B. O. and Jakesz R. 2008 Breast cancer issues in developing countries: an overview of the Breast Health Global Initiative. World J. Surg. 32, 2578–2585.CrossRefGoogle Scholar
  2. Bagheri F., Mesrian Tanha H., Mojtabavi Naeini M., Ghaedi K. and Azadeh M. 2016 Tumor-promoting function of single nucleotide polymorphism rs1836724 (C3388T) alters multiple potential legitimate microRNA binding sites at the \(3^{\prime }\)-untranslated region of ErbB4 in breast cancer. Mol. Med. Rep. 13, 4494–4498.CrossRefGoogle Scholar
  3. Bentwich I., Avniel A., Karov Y., Aharonov R., Gilad S., Barad O. et al. 2005 Identification of hundreds of conserved and nonconserved human microRNAs. Nat. Genet. 37, 766–770.CrossRefGoogle Scholar
  4. Chen Q.-H., Wang Q.-B. and Zhang B. 2014 Ethnicity modifies the association between functional microRNA polymorphisms and breast cancer risk: a HuGE meta-analysis. Tumor Biol. 35, 529–543.CrossRefGoogle Scholar
  5. Chou C.-H., Chang N.-W., Shrestha S., Hsu S.-D., Lin Y.-L., Lee W.-H. et al. 2015 miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database. Nucleic Acids Res. 44, D239–D247.CrossRefGoogle Scholar
  6. D’Angelo B., Benedetti E., Cimini A. and Giordano A. 2016 MicroRNAs: a puzzling tool in cancer diagnostics and therapy. Anticancer Res. 36, 5571–5575.CrossRefGoogle Scholar
  7. Dweep H. and Gretz N. 2015 miRWalk2. 0: a comprehensive atlas of microRNA-target interactions. Nat. Methods. 12, 697–697.CrossRefGoogle Scholar
  8. Griffiths-Jones S., Saini H. K., van Dongen S. and Enright A. J. 2007 miRBase: tools for microRNA genomics. Nucleic Acids Res. 36, D154–D158.CrossRefGoogle Scholar
  9. Ha M. and Kim V. N. 2014 Regulation of microRNA biogenesis. Nat. Rev. Mol. Cell Biol. 15, 509–524.CrossRefGoogle Scholar
  10. Hamosh A., Scott A. F., Amberger J. S., Bocchini C. A. and McKusick V. A. 2005 Online Mendelian Inheritance in Man (OMIM), a knowledge base of human genes and genetic disorders. Nucleic Acids Res. 33, D514–D517.CrossRefGoogle Scholar
  11. Harvey H., Piskareva O., Creevey L., Alcock L. C., Buckley P. G., O’Sullivan M. J. et al. 2015 Modulation of chemotherapeutic drug resistance in neuroblastoma SK-N-AS cells by the neural apoptosis inhibitory protein and miR-520f. Int. J. Cancer 136, 1579–1588.CrossRefGoogle Scholar
  12. Hasanzadeh A., Mesrian Tanha H., Ghaedi K. and Madani M. 2016 Aberrant expression of miR-9 in benign and malignant breast tumors. Mol. Cell Probes. 30, 279–284.CrossRefGoogle Scholar
  13. Hashemi M., Sanaei S., Mashhadi M., Hashemi S., Taheri M. and Ghavami S. 2015 Association study of hsa-mir-603 rs11014002 polymorphism and risk of breast cancer in a sample of Iranian population. Cell Mol. Biol. (Noisy-le-grand). 61, 69–73.Google Scholar
  14. Hashemi M., Sanaei S., Rezaei M., Bahari G., Hashemi S., Mashhadi M. et al. 2016 miR-608 rs4919510 \(\text{ C }>\text{ G }\) polymorphism decreased the risk of breast cancer in an Iranian subpopulation. Exp. Oncol. 38, 57–59.PubMedGoogle Scholar
  15. Huang D. W., Sherman B. T. and Lempicki R. A. 2009 Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44–57.CrossRefGoogle Scholar
  16. Kabirizadeh S., Azadeh M., Mirhosseini M., Ghaedi K. and Mesrian Tanha H. 2016 The SNP rs3746444 within mir-499a is associated with breast cancer risk in Iranian population. J. Cell Immunother. Google Scholar
  17. Keklikoglou I., Koerner C., Schmidt C., Zhang J., Heckmann D., Shavinskaya A. et al. 2012 MicroRNA-520/373 family functions as a tumor suppressor in estrogen receptor negative breast cancer by targeting NF-\(\kappa \)B and TGF-\(\beta \) signaling pathways. Oncogene 31, 4150–4163.CrossRefGoogle Scholar
  18. Marjan M. N., Hamzeh M. T., Rahman E. and Sadeq V. 2014 A computational prospect to aspirin side effects: aspirin and COX-1 interaction analysis based on non-synonymous SNPs. Comput. Biol. Chem. 51, 57–62.CrossRefGoogle Scholar
  19. Mehskat M., Mesrian Tanha H., Mojtabavi Naeini M., Ghaedi K., Sanati M. H., Meshkat M. et al. 2016 Functional SNP in stem of mir-146a affect Her2 status and breast cancer survival. Cancer Biomark. 17, 213–222.CrossRefGoogle Scholar
  20. Mesrian Tanha H., Rahgozar S. and Mojtabavi Naeini M. 2017 ABCC4 functional SNP in the \(3^\prime \) splice acceptor site of exon 8 (G912T) is associated with unfavorable clinical outcome in children with acute lymphoblastic leukemia. Cancer Chemother. Pharmacol. 80, 109–117.CrossRefGoogle Scholar
  21. Mesrian Tanha H., Mojtabavi Naeini M., Rahgozar S., Moafi A. and Honardoost M. A. 2016 Integrative computational in-depth analysis of dysregulated miRNA-mRNA interactions in drug-resistant pediatric acute lymphoblastic leukemia cells: an attempt to obtain new potential gene-miRNA pathways involved in response to treatment. Tumor Biol. 37, 7861–7872.CrossRefGoogle Scholar
  22. Omrani M., Hashemi M., Eskandari-Nasab E., Hasani S.-S., Mashhadi M. A., Arbabi F. et al. 2014 hsa-mir-499 rs3746444 gene polymorphism is associated with susceptibility to breast cancer in an Iranian population. Biomarkers 8, 259–267.CrossRefGoogle Scholar
  23. Ryan B. M., Robles A. I. and Harris C. C. 2010 Genetic variation in microRNA networks: the implications for cancer research. Nat. Rev. Cancer. 10, 389–402.CrossRefGoogle Scholar
  24. Salek R., Shahidsales S. and Mozafari V. 2016 Changing pattern in the clinical presentation of breast cancer in the absence of a screening program over a period of thirty-three years in Iran. The Breast 28, 95–99.CrossRefGoogle Scholar
  25. Sanaei S., Hashemi M., Rezaei M., Hashemi S. M., Bahari G. and Ghavami S. 2016 Evaluation of the pri-miR-34b/c rs4938723 polymorphism and its association with breast cancer risk. Biomed. Rep. 5, 125–129.CrossRefGoogle Scholar
  26. Srinivasan S., Clements J. A. and Batra J. 2016 Single nucleotide polymorphisms in clinics: fantasy or reality for cancer? Crit. Rev. Clin. Lab Sci. 53, 29–39.CrossRefGoogle Scholar
  27. Zhang B., Pan X., Cobb G. P. and Anderson T. A. 2007 microRNAs as oncogenes and tumor suppressors. Dev. Biol. 302, 1–12.CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2018

Authors and Affiliations

  • Marzieh Meshkat
    • 1
  • Hamzeh Mesrian Tanha
    • 2
  • Kamran Ghaedi
    • 2
    Email author
  • Mahboobeh Meshkat
    • 1
  1. 1.Department of Biology, Division of Cellular and Molecular BiologyNourdanesh University of MeymehMeymeh, IsfahanIran
  2. 2.Cellular and Molecular Biology Division, Biology Department, Faculty of SciencesUniversity of IsfahanIsfahanIran

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