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.
Similar content being viewed by others
References
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.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.
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.
Bretscher P, Cohn M. A theory of self-nonself discrimination. Science. 1970;169:1042–9.
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.
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.
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.
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.
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.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.
Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33.
Carthew RW. Gene regulation by microRNAs. Curr Opin Genet Dev. 2006;16:203–8.
Cai Y, Yu X, Hu S, Yu J. A brief review on the mechanisms of miRNA regulation. Genomics Proteomics Bioinform. 2009;7:147–54.
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.
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.
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.
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.
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.
Schwartz RH. A cell culture model for T lymphocyte clonal anergy. Science. 1990;248:1349–56.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
Corresponding authors
Additional information
Ruirong Wu and Fuchao Li contributed equally to this work.
Rights and permissions
About this article
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
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12032-014-0060-2