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Four Common Polymorphisms in MicroRNAs and the Risk of Adult Glioma in a Chinese Case–control Study

Abstract

Emerging evidence has shown that microRNAs (miRNAs) participate in human carcinogenesis as tumor suppressors or oncogenes. It has been suggested that four common single nucleotide polymorphisms (SNPs; miR-146aG > C, 149C > T, 196a2C > T, and 499A > G) are associated with susceptibility to numerous malignancies. However, published results are inconsistent and inclusive. To further investigate the role of these loci, we examined the association of the miRNA polymorphisms with the risk of gliomas in a Han population in northeastern China. Both miR-146aG > C and 196a2C > T showed allelic differences between glioma patients and healthy controls in the studied population, with an OR of 1.30 (P = 0.0006) and an odds ratio (OR) of 1.25 (P = 0.003), respectively. Logistic regression analysis also revealed that the 146aG > C and 196a2C > T wild-type homozygous carriers had an increased glioma risk compared to the variant carriers. Besides, in pairwise comparisons two SNP combinations were associated with the risk of glioma. Among others, carriers of both homozygous risk genotypes, i.e., 146aGG and 196a2CC were associated with a nearly 4-fold increased risk of glioma (OR = 3.77, P = 1.3 × 10−4). Overall, glioma risk increased with increasing numbers of risk variant alleles. These results suggest that the miR-146aG > C and 196a2C > T might influence the risk of developing glioma in a northeastern Han Chinese population.

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References

  • Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355

    PubMed  Article  CAS  Google Scholar 

  • Atkinson GP, Nozell SE, Benveniste ET (2010) NF-kappaB and STAT3 signaling in glioma: targets for future therapies. Expert Rev Neurother 10:575–586

    PubMed  Article  CAS  Google Scholar 

  • Bloomston M, Frankel WL, Petrocca F, Volinia S, Alder H, Hagan JP et al (2007) MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA 297:1901–1908

    PubMed  Article  CAS  Google Scholar 

  • Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G et al (2005) Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun 334:1351–1358

    PubMed  Article  CAS  Google Scholar 

  • Dou T, Wu Q, Chen X, Ribas J, Ni X, Tang C et al (2010) A polymorphism of microRNA196a genome region was associated with decreased risk of glioma in Chinese population. J Cancer Res Clin Oncol 136:1853–1859

    PubMed  Article  CAS  Google Scholar 

  • Garcia AI, Buisson M, Bertrand P, Rimokh R, Rouleau E, Lopez BS et al (2011) Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers. EMBO Mol Med 3:279–290

    PubMed  Article  CAS  Google Scholar 

  • Garzon R, Marcucci G, Croce CM (2010) Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev 9:775–789

    Article  CAS  Google Scholar 

  • Gu J, Liu Y, Kyritsis AP, Bondy ML (2009) Molecular epidemiology of primary brain tumors. Neurotherapeutics 6:427–435

    PubMed  Article  CAS  Google Scholar 

  • Guo H, Wang K, Xiong G, Hu H, Wang D, Xu X et al (2010) A functional variant in microRNA-146a is associated with risk of esophageal squamous cell carcinoma in Chinese Han. Familial Cancer 9:599–603

    PubMed  Article  Google Scholar 

  • He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S et al (2005) The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA 102:19075–19080

    PubMed  Article  CAS  Google Scholar 

  • Hoffman AE, Zheng T, Yi C, Leaderer D, Weidhaas J, Slack F et al (2009) microRNA miR-196a-2 and breast cancer: a genetic and epigenetic association study and functional analysis. Cancer Res 69:5970–5977

    PubMed  Article  CAS  Google Scholar 

  • Hu Z, Liang J, Wang Z, Tian T, Zhou X, Chen J et al (2009) Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women. Hum Mutat 30:79–84

    PubMed  Article  CAS  Google Scholar 

  • Hung PS, Chang KW, Kao SY, Chu TH, Liu CJ, Lin SC (2012) Association between the rs2910164 polymorphism in pre-mir-146a and oral carcinoma progression. Oral Oncol 48:404–408

    PubMed  Article  CAS  Google Scholar 

  • Jazdzewski K, Liyanarachchi S, Swierniak M, Pachucki J, Ringel MD, Jarzab B et al (2009) Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer. Proc Natl Acad Sci USA 106:1502–1505

    PubMed  Article  CAS  Google Scholar 

  • Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A (2008) Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci USA 105:7269–7274

    PubMed  Article  CAS  Google Scholar 

  • Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009 CA: a. Cancer J Clin 59:225–249

    Article  Google Scholar 

  • Jin L, Su B (2000) Natives or immigrants: modern human origin in east Asia. Nat Rev Genet 1:126–133

    PubMed  Article  CAS  Google Scholar 

  • Kanai M, Hamada J, Takada M, Asano T, Murakawa K, Takahashi Y et al (2010) Aberrant expressions of HOX genes in colorectal and hepatocellular carcinomas. Oncol Rep 23:843–851

    PubMed  CAS  Google Scholar 

  • Kefas B, Godlewski J, Comeau L, Li Y, Abounader R, Hawkinson M et al (2008) microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma. Cancer Res 68:3566–3572

    PubMed  Article  CAS  Google Scholar 

  • Kozomara A, Griffiths-Jones S (2011) miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 39:D152–157

    PubMed  Article  CAS  Google Scholar 

  • Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T (2007) Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 39:673–677

    PubMed  Article  CAS  Google Scholar 

  • Li XD, Li ZG, Song XX, Liu CF (2010a) A variant in microRNA-196a2 is associated with susceptibility to hepatocellular carcinoma in Chinese patients with cirrhosis. Pathology 42:669–673

    PubMed  Article  CAS  Google Scholar 

  • Li Y, Vandenboom TG 2nd, Wang Z, Kong D, Ali S, Philip PA et al (2010b) miR-146a suppresses invasion of pancreatic cancer cells. Cancer Res 70:1486–1495

    PubMed  Article  CAS  Google Scholar 

  • Lin SL, Chiang A, Chang D, Ying SY (2008) Loss of mir-146a function in hormone-refractory prostate cancer. RNA (New York, NY 14:417–424

  • Luthra R, Singh RR, Luthra MG, Li YX, Hannah C, Romans AM et al (2008) MicroRNA-196a targets annexin A1: a microRNA-mediated mechanism of annexin A1 downregulation in cancers. Oncogene 27:6667–6678

    PubMed  Article  CAS  Google Scholar 

  • Ma L, Teruya-Feldstein J, Weinberg RA (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449:682–688

    PubMed  Article  CAS  Google Scholar 

  • Maschler S, Gebeshuber CA, Wiedemann EM, Alacakaptan M, Schreiber M, Custic I et al (2010) Annexin A1 attenuates EMT and metastatic potential in breast cancer. EMBO Mol Med 2:401–414

    PubMed  Article  CAS  Google Scholar 

  • Mei J, Bachoo R, Zhang CL (2011) MicroRNA-146a inhibits glioma development by targeting Notch1. Mol Cell Biol 31:3584–3592

    PubMed  Article  CAS  Google Scholar 

  • Michael MZ, O’Connor SM, van Holst Pellekaan NG, Young GP, James RJ (2003) Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 1:882–891

    PubMed  CAS  Google Scholar 

  • Okubo M, Tahara T, Shibata T, Yamashita H, Nakamura M, Yoshioka D et al (2011) Association study of common genetic variants in pre-microRNAs in patients with ulcerative colitis. J Clin Immunol 31:69–73

    PubMed  Article  CAS  Google Scholar 

  • Owens BM, Hawley RG (2002) HOX and non-HOX homeobox genes in leukemic hematopoiesis. Stem cells (Dayton, Ohio) 20:364–379

    Google Scholar 

  • Parkin DM (2002) Cancer incidence in five continents. Volume VIII. IARC Scientific Publications, pp 1–781

  • Peng S, Kuang Z, Sheng C, Zhang Y, Xu H, Cheng Q (2009) Association of microRNA-196a-2 gene polymorphism with gastric cancer risk in a Chinese population. Dig Dis Sci 55:2288–2293

    PubMed  Article  Google Scholar 

  • Permuth-Wey J, Thompson RC, Burton Nabors L, Olson JJ, Browning JE, Madden MH et al (2011) A functional polymorphism in the pre-miR-146a gene is associated with risk and prognosis in adult glioma. J Neuro Oncol 105:639–646

    Article  CAS  Google Scholar 

  • Ponomarev ED, Veremeyko T, Barteneva N, Krichevsky AM, Weiner HL (2011) MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-alpha-PU.1 pathway. Nat Med 17:64–70

    PubMed  Article  CAS  Google Scholar 

  • Purcell S, Cherny SS, Sham PC (2003) Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics (Oxford, England) 19:149–150

  • Qi P, Dou TH, Geng L, Zhou FG, Gu X, Wang H et al (2010) Association of a variant in MIR 196A2 with susceptibility to hepatocellular carcinoma in male Chinese patients with chronic hepatitis B virus infection. Hum Immunol 71:621–626

    PubMed  Article  CAS  Google Scholar 

  • Ron E, Modan B, Boice JD Jr, Alfandary E, Stovall M, Chetrit A et al (1988) Tumors of the brain and nervous system after radiotherapy in childhood. New Engl J Med 319:1033–1039

    PubMed  Article  CAS  Google Scholar 

  • Saba R, Goodman CD, Huzarewich RL, Robertson C, Booth SA (2008) A miRNA signature of prion induced neurodegeneration. PLoS One 3:e3652

    PubMed  Article  Google Scholar 

  • Shen J, Ambrosone CB, DiCioccio RA, Odunsi K, Lele SB, Zhao H (2008) A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis 29:1963–1966

    PubMed  Article  CAS  Google Scholar 

  • Shete S, Hosking FJ, Robertson LB, Dobbins SE, Sanson M, Malmer B et al (2009) Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet 41:899–904

    PubMed  Article  CAS  Google Scholar 

  • Taganov KD, Boldin MP, Chang KJ, Baltimore D (2006) NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 103:12481–12486

    PubMed  Article  CAS  Google Scholar 

  • Tian T, Shu Y, Chen J, Hu Z, Xu L, Jin G et al (2009) A functional genetic variant in microRNA-196a2 is associated with increased susceptibility of lung cancer in Chinese. Cancer Epidemiol Biomarkers Prev 18:1183–1187

    PubMed  Article  CAS  Google Scholar 

  • Wang X, Tang S, Le SY, Lu R, Rader JS, Meyers C et al (2008) Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS One 3:e2557

    PubMed  Article  Google Scholar 

  • Wrensch M, Jenkins RB, Chang JS, Yeh RF, Xiao Y, Decker PA et al (2009) Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nat Genet 41:905–908

    PubMed  Article  CAS  Google Scholar 

  • Xiao C, Rajewsky K (2009) MicroRNA control in the immune system: basic principles. Cell 136:26–36

    PubMed  Article  CAS  Google Scholar 

  • Xu B, Feng NH, Li PC, Tao J, Wu D, Zhang ZD et al (2010) A functional polymorphism in Pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo. Prostate 70:467–472

    PubMed  Article  CAS  Google Scholar 

  • Xu J, Hu Z, Xu Z, Gu H, Yi L, Cao H et al (2009a) Functional variant in microRNA-196a2 contributes to the susceptibility of congenital heart disease in a Chinese population. Hum Mutat 30:1231–1236

    PubMed  Article  CAS  Google Scholar 

  • Xu S, Yin X, Li S, Jin W, Lou H, Yang L et al (2009b) Genomic dissection of population substructure of Han Chinese and its implication in association studies. Am J Hum Genet 85:762–774

    PubMed  Article  CAS  Google Scholar 

  • Xu T, Zhu Y, Wei QK, Yuan Y, Zhou F, Ge YY et al (2008) A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis 29:2126–2131

    PubMed  Article  CAS  Google Scholar 

  • Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M et al (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9:189–198

    PubMed  Article  CAS  Google Scholar 

  • Yom CK, Han W, Kim SW, Kim HS, Shin HC, Chang JN et al (2011) Clinical significance of annexin A1 expression in breast cancer. J Breast Cancer 14:262–268

    PubMed  Article  Google Scholar 

  • Zeng Y, Sun QM, Liu NN, Dong GH, Chen J, Yang L et al (2010) Correlation between pre-miR-146a C/G polymorphism and gastric cancer risk in Chinese population. World J Gastroenterol 16:3578–3583

    PubMed  Article  CAS  Google Scholar 

  • Zhou F, Zhu H, Luo D, Wang M, Dong X, Hong Y et al (2012) A functional polymorphism in pre-miR-146a is associated with susceptibility to gastric cancer in a Chinese population. DNA Cell Biol 31:1290–1295

    PubMed  Article  CAS  Google Scholar 

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Acknowledgements

We gratefully acknowledge the numerous sample donors for making this work possible. This work was funded by the National Natural Science Foundation of China (81172742).

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Correspondence to Enzhong Liu.

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Enxi Hu and Dianhong Wang equally contributed to this work.

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Hu, E., Wang, D., Zhang, X. et al. Four Common Polymorphisms in MicroRNAs and the Risk of Adult Glioma in a Chinese Case–control Study. J Mol Neurosci 51, 933–940 (2013). https://doi.org/10.1007/s12031-013-9980-0

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  • DOI: https://doi.org/10.1007/s12031-013-9980-0

Keywords

  • MicroRNA
  • Glioma
  • SNP
  • Chinese
  • Case–control study
  • Polymorphisms