Inferring Single Nucleotide Polymorphisms in MicroRNA Binding Sites of Lung Cancer-related Inflammatory Genes

  • He, Fei (Department of Epidemiology, School of Public Health, Fujian Medical University) ;
  • Zheng, Ling-Ling (Department of Prevention and Health Care, FuJian Medical University Uion Hospital) ;
  • Luo, Wen-Ting (Department of Chronic and Endemic Disease Control, Xiamen Center for Disease Control and Prevention) ;
  • Yang, Rong (Department of Medical Record Management, FuJian Medical University Uion Hospital) ;
  • Xu, Xiao-Qin (School Office, School of Nursing, Fujian Medical University) ;
  • Cai, Lin (Department of Epidemiology, School of Public Health, Fujian Medical University)
  • Published : 2014.04.30


Single nucleotide polymorphisms located at microRNA (miRNA)-binding sites are likely to affect the expression of miRNA targets and may contribute to the susceptibility of humans to common diseases. Here 335 candidate lung cancer-related inflammatory genes were selected according to the existing literature and database. We identified putative miRNA-binding sites of 149 genes by specialised algorithms and screened SNPs in the 3'UTRs of these genes. By calculating binding free energy, we sorted 269 SNPs on the basis of the possibility of prediction. The proposed approach could help to easy the identification of functionally relevant SNPs and minimize the workflow and the costs.


  1. Shen N, Gong T, Wang JD, et al (2011). Cigarette smoke-induced pulmonary inflammatory responses are mediated by EGR-1/GGPPS/MAPK signaling. Am J Pathol, 178, 110-8.
  2. Ohnishi S, Ma N, Thanan R, et al (2013). DNA damage in inflammation-related carcinogenesis and cancer stem cells. Oxid Med Cell Longev, 387014.
  3. Richardson K, Lai CQ, Parnell LD, et al (2011). A genome-wide survey for SNPs altering microRNA seed sites identifies functional candidates in GWAS. BMC Genomics, 12, 504.
  4. Saunders MA, Liang H, Li WH (2007). Human polymorphism at microRNAs and microRNA target sites. Proc Natl Acad Sci USA, 104, 3300-5.
  5. Song CQ, Zhang JH, Shi JC, et al (2014). Bioinformatic prediction of SNPs within miRNA binding sites of inflammatory genes associated with gastric cancer. Asian Pac J Cancer Pre, 15, 937-43.
  6. Tomari Y, Zamore PD (2005). Perspective: machines for RNAi. Genes Dev, 19, 517-29.
  7. Wu Y, Xiao Y, Ding X, et al (2011). A miR-200b/200c/429-binding site polymorphism in the 3’ untranslated region of the AP-2alpha gene is associated with cisplatin resistance. PLoS ONE, 6, 29043.
  8. Yu H, Zhao H, Wang LE, et al (2011). An analysis of single nucleotide polymorphisms of 125 DNA repair genes in the Texas genome-wide association study of lung cancer with a replication for the XRCC4 SNPs. DNA Repair, 10, 398-407.
  9. Zhang W, Edwards A, Zhu D, et al (2012). miRNA-mediated relationships between Cis-SNP genotypes and transcript intensities in lymphocyte cell lines. PLoS One, 7, 31429.
  10. Zu Y, Ban J, Xia Z, et al (2013). Genetic variation in a miR-335 binding site in BIRC5 alters susceptibility to lung cancer in Chinese Han populations. Biochem Biophys Res Commun, 430, 529-34.
  11. John B, Enright AJ, Aravin A, et al (2004). Human MicroRNA targets. PLoS Biol, 2, 363.
  12. Houghton AM, Mouded M, Shapiro SD (2008). Common origins of lung cancer and COPD. Nat Med, 14, 1023-4.
  13. Hussain SP, Harris CC (2007). Inflammation and cancer: an ancient link with novel potentials. Int J Cancer, 121, 2373-80.
  14. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
  15. Kim M, Chen X, Chin LJ, et al (2014). Extensive sequence variation in the 3' untranslated region of the KRAS gene in lung and ovarian cancer cases. Cell Cycle, 13.
  16. Lagos-Quintana M, Rauhut R, Lendeckel W, et al (2001). Identification of novel genes coding for small expressed RNAs. Science, 294, 853-8.
  17. Lee G, Walser TC, Dubinett SM (2009). Chronic inflammation, chronic obstructive pulmonary disease, and lung cancer. Curr Opin Pulm Med, 15, 303-7.
  18. Lee J, Taneja V, Vassallo R (2012). Cigarette smoking and inflammation: cellular and molecular mechanisms. J Dent Res, 91, 142-9.
  19. Liu C, Zhang F, Li T, et al (2012). MirSNP, a database of polymorphisms altering miRNA target sites, identifies miRNA-related SNPs in GWAS SNPs and eQTLs. BMC Genomics, 13, 661.
  20. McMillan DH, Baglole CJ, Thatcher TH, et al (2011). Lungtargeted overexpression of the NF-kappaB member RelB inhibits cigarette smoke-induced inflammation. Am J Pathol, 179, 125-33.
  21. Mishra PJ1, Bertino JR (2009). MicroRNA polymorphisms: the future of pharmacogenomics, molecular epidemiology and individualized medicine. Pharmacogenomics, 10, 399-416.
  22. Betel D, Koppal A, Agius P, et al (2010). Comprehensive modeling of microRNA targets predicts functional nonconserved and non-canonical sites. Genome Biol, 11, 90.
  23. Bhat IA, Pandith AA, Bhat BA, et al (2013). Lack of association of a common polymorphism in the 3'-UTR of interleukin 8 with non small cell lung cancer in Kashmir. Asian Pac J Cancer Prev, 14, 4403-8.
  24. Chen Z, Xu L, Ye X, et al (2013). Polymorphisms of microRNA sequences or binding sites and lung cancer: a meta-analysis and systematic review. PLoS One, 8, 61008.
  25. Cheng M, Yang L, Yang R, et al (2013). A microRNA-135a/b binding polymorphism in CD133 confers decreased risk and favorable prognosis of lung cancer in Chinese by reducing CD133 expression. Carcinogenesis, 34, 2292-9.
  26. Cho WC, Kwan CK, Yau S, et al (2011). The role of inflammation in the pathogenesis of lung cancer. Expert Opin Ther Targets, 15, 1127-37.
  27. Coussens LM, Werb Z (2002). Inflammation and cancer. Nature, 420, 860-7.
  28. Ding J, Gao Y, He Y, et al (2011). Screening SNPs residing in the microRNA-binding sites of hepatocellular carcinoma related genes. Int J Data Min Bioinform, 5, 1-21.
  29. Grivennikov SI, Greten FR, Karin M (2010). Immunity, inflammation, and cancer. Cell, 140, 883-99.
  30. Hattar K, Savai R, Subtil FS, et al (2013). Endotoxin induces proliferation of NSCLC in vitro and in vivo: role of COX-2 and EGFR activation. Cancer Immunol Immunothe, 62, 309-20.
  31. Hariharan M, Scaria V, Brahmachari SK. dbSMR: a novel resource of genome-wide SNPs affecting microRNA mediated regulation. BMC Bioinformatics, 10, 108.

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