Skip to main content

Advertisement

SpringerLink
Log in

A functional variant at miR-132-3p, miR-212-3p, and miR-361-5p binding site in CD80 gene alters susceptibility to gastric cancer in a Chinese Han population

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

A number of single-nucleotide polymorphisms within the 3′-UTR of genes have been shown to relate to the occurrence of cancers. In this study, by using polymerase chain reaction–restriction fragment length analysis method, we determined an SNP rs1599795 in the 3′-UTR of CD80 gene in 183 gastric cancer patients and 348 healthy controls. Statistical analysis results showed that SNP rs1599795 genotypes were significantly correlated with the risk of gastric cancer. Compared with the AA homozygotes, the TA heterozygotes were significantly more prevalent in the patients (OR 1.44, 95 % CI 0.98–2.11) with a larger tumor size (P = 0.001), deeper infiltration (P = 1.5 × 10−5), higher possibility of lymph node metastasis (P = 0.003), and more in the late stage (TNM stage III and IV; P = 0.003); the TT homozygotes had larger tumor size (P = 0.001) and lower degree of differentiation (P = 2.2 × 10−4). Dual-luciferase reporter assays showed that miR-132-3p, miR-212-3p, and miR-361-5p inhibited the expression of CD80 through binding with the CD80 3′-UTR, and this inhibitory role of miR-132-3p, miR-212-3p, and miR-361-5p was impacted by rs1599795. Our findings have shown that the SNP rs1599795 in CD80 3′-UTR, through disrupting the regulatory role of miR-132-3p, miR-212-3p, and miR-361-5p in CD80 expression, contributed to the occurrence of gastric cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Sunami T, Yashiro M, Chung KH. ICAM-1 (intercellular adhesion molecule-1) gene transfection inhibits lymph node metastasis by human gastric cancer cells. Jpn J Cancer Res. 2000;91:925–33.

    Article  CAS  PubMed  Google Scholar 

  2. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.

    Article  PubMed  Google Scholar 

  3. Wu WK, Lee CW, Cho CH, Fan D, Wu K, Yu J, et al. MicroRNA dysregulation in gastric cancer: a new player enters the game. Oncogene. 2010;29:5761–71.

    Article  CAS  PubMed  Google Scholar 

  4. Bretscher P, Cohn M. A theory of self-nonself discrimination. Science. 1970;169:1042–9.

    Article  CAS  PubMed  Google Scholar 

  5. Bhatia S, Edidin M, Almo SC, Nathenson SG. B7-1 and B7-2: similar costimulatory ligands with different biochemical, oligomeric and signaling properties. Immunol Lett. 2006;104:70–5.

    Article  CAS  PubMed  Google Scholar 

  6. Si L, Si H, Chen Y, Sun Y, Wing Y. B7-1 antigen expression in tumor cells from cancerous human tissues. Anal Quant Cytol Histol. 1999;21:521–6.

    CAS  PubMed  Google Scholar 

  7. Wu TC, Huang AY, Jaffee EM, Levitsky HI, Pardoll DM. A reassessment of the role of B7-1 expression in tumor rejection. J Exp Med. 1995;182:1415–21.

    Article  CAS  PubMed  Google Scholar 

  8. Koyama S, Maruyama T, Adachi S, Nozue M. Expression of costimulatory molecules, B7-1 and B7-2 on human gastric carcinoma. J Cancer Res Clin Oncol. 1998;124:383–8.

    Article  CAS  PubMed  Google Scholar 

  9. Scarpa M, Bortolami M, Cecchetto A, Faggian D, Kotsafti A, Ruffolo C, et al. Mucosal immune environment in colonic carcinogenesis: CD80 up-regulation in colonic dysplasia in ulcerative colitis. Eur J Cancer. 2011;47:611–9.

    Article  CAS  PubMed  Google Scholar 

  10. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  CAS  PubMed  Google Scholar 

  11. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Carthew RW. Gene regulation by microRNAs. Curr Opin Genet Dev. 2006;16:203–8.

    Article  CAS  PubMed  Google Scholar 

  13. Cai Y, Yu X, Hu S, Yu J. A brief review on the mechanisms of miRNA regulation. Genomics Proteomics Bioinform. 2009;7:147–54.

    Article  CAS  Google Scholar 

  14. Wu D, Wang F, Dai WQ, He L, Lu J, Xu L, et al. The miR-146a rs2910164 G > C polymorphism and susceptibility to digestive cancer in Chinese. Asian Pac J Cancer Prev. 2013;14:399–403.

    Article  PubMed  Google Scholar 

  15. Wang WP, Li F, Mao Y, Zhou H, Sun J, Li R, et al. A miR-570 binding-site polymorphism in the B7-H1 gene is associated with the risk of gastric adenocarcinoma. Hum Genet. 2013;132:641–8.

    Article  CAS  PubMed  Google Scholar 

  16. Yang P, Tang R, Zhu J, Zou L, Wu R, Zhou H, et al. A functional variant at miR-24 binding site in B7-H2 alters susceptibility to gastric cancer in a Chinese Han population. Mol Immunol. 2013;56:98–103.

    Article  CAS  PubMed  Google Scholar 

  17. Linsley PS, Brady W, Grosmaire L, Aruffo A, Damle NK, Ledbetter JA. Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation. J Exp Med. 1991;173:721–30.

    Article  CAS  PubMed  Google Scholar 

  18. Fujii H, Inobe M, Kimura F, Murata J, Murakami M, Onishi Y, et al. Vaccination of tumor cells transfected with the B7-1 (CD80) gene induces the anti-metastatic effect and tumor immunity in mice. Int J Cancer. 1996;66:24–219.

    Article  Google Scholar 

  19. Schwartz RH. A cell culture model for T lymphocyte clonal anergy. Science. 1990;248:1349–56.

    Article  CAS  PubMed  Google Scholar 

  20. Chen XL, Cao XD, Kang AJ, Wang KM, Su BS, Wang YL. In situ expression and significance of B7 costimulatory molecules within tissues of human gastric carcinoma. World J Gastroenterol. 2003;9:1370–3.

    CAS  PubMed  Google Scholar 

  21. Mishra PJ, Banerjee D, Bertino JR. miRSNPs or miR-polymorphisms, new players in microRNA mediated regulation of the cell: introducing microRNA pharmacogenomics. Cell Cycle. 2008;7:853–8.

    Article  CAS  PubMed  Google Scholar 

  22. Park J-K, Henry JC, Jiang J, Esau C, Gusev Y, Lerner MR, et al. miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor. Biochem Biophys Res Commun. 2011;406:518–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 2006;103:2257–61.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9:189–98.

    Article  CAS  PubMed  Google Scholar 

  25. Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 2008;299:425–36.

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Wu WY, Xue XY, Chen ZJ, Han SL, Huang YP, Zhang LF, et al. Potentially predictive microRNAs of gastric cancer with metastasis to lymph node. World J Gastroenterol. 2011;17:3645–51.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Xu L, Wang F, Xu XF, Mo WH, Xia YJ, Wan R, et al. Down-regulation of miR-212 expression by DNA hypermethylation in human gastric cancer cells. Med Oncol. 2011;1:189–96.

    Article  Google Scholar 

  28. Wada R, Akiyama Y, Hashimoto Y, Fukamachi H, Yuasa Y. MiR-212 is downregulated and suppresses methyl-CpG-binding protein MeCP2 in human gastric cancer. Int J Cancer. 2010;127:1106–14.

    Article  CAS  PubMed  Google Scholar 

  29. Song Tao, Xia Wei, Ningsheng Shao X, Zhang CW, Yiguang W, et al. Differential miRNA expression profiles in bladder urothelial carcinomas. Asian Pacific J Cancer Prev. 2010;11:905–11.

    Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81270031), the Natural Science Foundation of the Higher Education Institutions of Jiangsu Province (No. 12KJB320012), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Wuxi, 214062, China

    Ruirong Wu, Qinghua Qi & Dong Hua

  2. Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China

    Jianjie Zhu, Rong Tang, Xinru Zhou & Weipeng Wang

  3. Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China

    Fuchao Li, Rui Li & Weichang Chen

Authors
  1. Ruirong Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fuchao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jianjie Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rong Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qinghua Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xinru Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Weipeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Dong Hua
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Weichang Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Dong Hua or Weichang Chen.

Additional information

Ruirong Wu and Fuchao Li contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, R., Li, F., Zhu, J. et al. A functional variant at miR-132-3p, miR-212-3p, and miR-361-5p binding site in CD80 gene alters susceptibility to gastric cancer in a Chinese Han population. Med Oncol 31, 60 (2014). https://doi.org/10.1007/s12032-014-0060-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0060-2

Keywords

Search

Navigation