Abstract
Single-nucleotide polymorphisms (SNPs) in the promoter region of long intergenic non-coding RNAs (lincRNAs) could play a regulatory role in its expression level and then get involved in colorectal cancer (CRC). Thus, we conducted a two-stage case–control study to investigate the associations of Tag SNPs within the promoter region of selected lincRNAs from microarray data with risk of CRC. A total of 320 cases and 319 controls were recruited in the test set to explore the associations between 16 SNPs with no deviations from Hardy–Weinberg equilibrium (HWE) and risk of CRC. Furthermore, 501 cases and 538 controls were included as the validation set to confirm the significant associations. RP11-3N2.1 rs13230517 polymorphism was found to be negatively associated with CRC in both test set (AA vs. GG, OR = 0.68, 95% CI = 0.48–0.96) and validation set (AA vs. GG, OR = 0.76, 95% CI = 0.59–0.98). Pooled analysis showed that individuals with GA/AA genotypes had a significantly decreased risk of CRC when compared with those carrying GG genotype (OR = 0.74, 95% CI = 0.60–0.90) in the combined set. The crossover analysis revealed that rs13230517 GA/AA carriers had a decreased risk of CRC than GG carriers among non-drinkers in both test and combined set. However, no gene-environment multiplicative interactions were found on risk of CRC. Our findings suggest that rs13230517 polymorphism might participate in the pathogenesis of CRC and have the potential to be a biomarker for predicting the risk of CRC.
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References
Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10:155–9.
Chen G, Wang ZY, Wang DQ, Qiu CX, Liu MX, Chen X, et al. LncRNADisease: a database for long-non-coding RNA-associated diseases. Nucleic Acids Res. 2013;41:D983–D986.
Yang F, Bi JW, Xue XC, Zheng LM, Zhi KK, Hua JD, et al. Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells. FEBS J. 2012;279:3159–65.
Gutschner T, Hammerle M, Eissmann M, Hsu J, Kim Y, Hung G, et al. The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res. 2013;73:1180–9.
Nie Y, Liu X, Qu SH, Song E, Zou H, Gong C. Long non-coding RNA HOTAIR is an independent prognostic marker for nasopharyngeal carcinoma progression and survival. Cancer Sci. 2013;104:458–64.
St-Laurent G, Wahlestedt C, Kapranov P. The landscape of long noncoding RNA classification. Trends Genet. 2015;31:239–51.
Tsai MC, Spitale RC, Chang HY. Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res. 2011;71:3–7.
Gibb EA, Brown CJ, Lam WL. The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 2011;10:38.
Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010;142:409–19.
Szafron LM, Balcerak A, Grzybowska EA, Pienkowska-Grela B, Podgorska A, Zub R, et al. The putative oncogene, CRNDE, is a negative prognostic factor in ovarian cancer patients. Oncotarget. 2015;6:43897–910.
Jendrzejewski J, He HL, Radomska HS, Li W, Tomsic J, Liyanarachchi S, et al The polymorphism rs944289 predisposes to papillary thyroid carcinoma through a large intergenic noncoding RNA gene of tumor suppressor type. Proc Natl Acad Sci USA. 2012;109:8646–51.
Zanke BW, Greenwood CMT, Rangrej J, Kustra R, Tenesa A, Farrington SM, et al. Genome-wide association scan identifies a colorectal cancer susceptibility locus on chromosome 8q24. Nat Genet. 2007;39:989–94.
Nan HM, Hutter CM, Lin Y, Jacobs EJ, Ulrich CM, White E, et al. Association of aspirin and NSAID use with risk of colorectal cancer according to genetic variants. JAMA. 2015;313:1133–42.
Houlston RS, Cheadle J, Dobbins SE, Tenesa A, Jones AM, Howarth K, et al. Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33. Nat Genet. 2010;42:973–89.
Cui R, Okada Y, Jang SG, Ku JL, Park JG, Kamatani Y, et al Common variant in 6q26-q27 is associated with distal colon cancer in an Asian population. Gut. 2011;60:799–805.
Jing FY, Jin HC, Mao YY, Li YJ, Ding Y, Fan CH, et al. Genome-wide analysis of long non-coding RNA expression and function in colorectal cancer. Tumor Biol. 2017;39:1010428317703650.
Zhang YJ, Liu B, Jin MJ, Ni Q, Liang X, Ma XY, et al. Genetic polymorphisms of transforming growth factor-beta 1 and its receptors and colorectal cancer susceptibility: a population-based case-control study in China. Cancer Lett. 2009;275:102–8.
Nasiri H, Forouzandeh M, Rasaee MJ, Rahbarizadeh F. Modified salting-out method: High-yield, high-quality genomic DNA extraction from whole blood using laundry detergent. J Clin Lab Anal. 2005;19:229–32.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–E386.
Guttman M, Rinn JL. Modular regulatory principles of large non-coding RNAs. Nature. 2012;482:339–46.
Zhai HY, Fesler A, Schee K, Fodstad O, Flatmark K, Ju JF. Clinical significance of long intergenic noncoding RNA-p21 in colorectal cancer. Clin Colorectal Cancer. 2013;12:261–6.
Nissan A, Stojadinovic A, Mitrani-Rosenbaum S, Halle D, Grinbaum R, Roistacher M, et al. Colon cancer associated transcript-1: a novel RNA expressed in malignant and pre-malignant human tissues. Int J Cancer. 2012;130:1598–606.
Alaiyan B, Ilyayev N, Stojadinovic A, Izadjoo M, Roistacher M, Pavlov V, et al. Differential expression of colon cancer associated transcript1 (CCAT1) along the colonic adenoma-carcinoma sequence. BMC Cancer. 2013;13:196.
Ye ZY, Zhou M, Tian B, Wu B, Li JC. Expression of IncRNA-CCAT1, E-cadherin and N-cadherin in colorectal cancer and its clinical significance. Int J Clin Exp Med. 2015;8:3707–15.
Han Y, Yang YN, Yuan HH, Zhang TT, Sui H, Wei XL, et al. UCA1, a long non-coding RNA up-regulated in colorectal cancer influences cell proliferation, apoptosis and cell cycle distribution. Pathology. 2014;46:396–401.
Backes C, Ludwig N, Leidinger P, Harz C, Hoffmann J, Keller A, et al. Immunogenicity of autoantigens. BMC Genomics. 2011;12:340.
Kijanka G, Hector S, Kay EW, Murray F, Cummins R, Murphy D, et al. Human IgG antibody profiles differentiate between symptomatic patients with and without colorectal cancer. Gut. 2010;59:69–78.
Xiang SL, Xiang TX, Xiao Q, Li YH, Shao BF, Luo T. Zinc-finger protein 545 is inactivated due to promoter methylation and functions as a tumor suppressor through the Wnt/β-catenin, PI3K/AKT and MAPK/ERK signaling pathways in colorectal cancer. Int J Oncol. 2017;51:801–11.
Jalali S, Bhartiya D, Lalwani MK, Sivasubbu S, Scaria V. Systematic transcriptome wide analysis of lncRNA-miRNA interactions. PLoS ONE. 2013;8:e53823.
He YQ, Wang JX, Wang J, Yung VY, Hsu E, Li A, et al. MicroRNA-135b regulates apoptosis and chemoresistance in colorectal cancer by targeting large tumor suppressor kinase 2. Am J Cancer Res. 2015;5:1382–95.
Valeri N, Braconi C, Gasparini P, Murgia C, Lampis A, Paulus-Hock V, et al. MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer. Cancer Cell. 2014;25:469–83.
Wu WY, Wang Z, Yang PC, Yang JF, Liang J, Chen YH, et al. MicroRNA-135b regulates metastasis suppressor 1 expression and promotes migration and invasion in colorectal cancer. Mol Cell Biochem. 2014;388:249–59.
Li JL, Liang HW, Bai M, Ning T, Wang C, Fan Q, et al. miR-135b promotes cancer progression by targeting transforming growth factor beta receptor II (TGFBR2) in colorectal cancer. PLoS ONE. 2015;10:e0145589.
Wang X, Arai S, Song X, Reichart D, Du K, Pascual G, et al. Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature. 2008;454:126–30.
Ning SW, Zhao ZXL, Ye JR, Wang P, Zhi H, Li RH, et al. LincSNP: a database of linking disease-associated SNPs to human large intergenic non-coding RNAs. BMC Bioinformatics. 2014;15:152.
Ko E, Seo HW, Jung ES, Kim BH, Jung G. The TERT promoter SNP rs2853669 decreases E2F1 transcription factor binding and increases mortality and recurrence risks in liver cancer. Oncotarget. 2016;7:684–99.
Liang PS, Chen TY, Giovannucci E. Cigarette smoking and colorectal cancer incidence and mortality: systematic review and meta-analysis. Int J Cancer. 2009;124:2406–15.
Fedirko V, Tramacere I, Bagnardi V, Rota M, Scotti L, Islami F, et al. Alcohol drinking and colorectal cancer risk: an overall and dose-response meta-analysis of published studies. Ann Oncol. 2011;22:1958–72.
Acknowledgements
This work was supported by the National Natural Science Foundation of China (no. 81373087, 81602917), the National Key Basic Research Program (973 program no. 2015CB554003) and the Natural Science Foundation of Zhejiang Province, China (no. LQ15H260001).
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Ye, D., Hu, Y., Jing, F. et al. A novel SNP in promoter region of RP11-3N2.1 is associated with reduced risk of colorectal cancer. J Hum Genet 63, 47–54 (2018). https://doi.org/10.1038/s10038-017-0361-3
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DOI: https://doi.org/10.1038/s10038-017-0361-3
