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Associations between polymorphisms of HOTAIR and risk of gastric cardia adenocarcinoma in a population of north China

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Tumor Biology

Abstract

As an important long noncoding RNA, Hox transcript antisense intergenic RNA (HOTAIR) is involved in the development and progression of various carcinomas. However, the role and genetic alterations of HOTAIR in gastric cardia adenocarcinoma (GCA) occurrence and progression have not been elucidated. We performed a case-control study in a population of north China to evaluate the possible association between haplotype-tagging SNPs (htSNPs) of the whole HOTAIR sequence and the risk of GCA as well as functional effect of the susceptibility single nucleotide polymorphism (SNP) rs12826786 on gene expression. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to examine the genotype of htSNPs in 515 GCA patients and 654 control subjects, and the quantitative real-time reverse transcription PCR (RT-PCR) method was used to examine the expression of HOTAIR in 102 GCA patients. A family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing GCA. Among three htSNPs of the HOTAIR gene (rs12826786 C>T, rs4759314 A>G, and rs10783618 C>T), only the T allele of rs12826786 was found to increase the risk of developing GCA and was associated with smoking habit and tumor-node-metastasis (TNM) stage. In addition, higher expression levels of HOTAIR were found in tumor tissues and rs12826786 SNP has a genotype-specific effect on HOTAIR expression. A high HOTAIR expression level was associated with poor GCA patients’ survival. These results indicate that functional genotype alteration of rs12826786 SNP may influence the expression of HOTAIR, and HOTAIR may be a useful marker to predict the biological behavior of tumors and potentially a therapeutic target in GCA treatment.

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References

  1. Crew KD, Neugut AI. Epidemiology of upper gastrointestinal malignancies. Semin Oncol. 2004;31:450–64.

    Article  PubMed  Google Scholar 

  2. Yang L. Incidence and mortality of gastric cancer in China. World J Gastroenterol. 2006;12:17–20.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ma JL, Zhang L, Brown LM, Li JY, Shen L, Pan KF, et al. Fifteen-year effects of Helicobacter pylori, garlic, and vitamin treatments on gastric cancer incidence and mortality. J Natl Cancer Inst. 2012;104:488–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. ENCODE Project Consortium, Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007;447:799–816.

    Article  Google Scholar 

  5. Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, et al. The transcriptional landscape of the mammalian genome. Science. 2005;309:1559–63.

    Article  CAS  PubMed  Google Scholar 

  6. Hoshino I, Matsubara H. MicroRNAs in cancer diagnosis and therapy: from bench to bedside. Surg Today. 2013;43:467–78.

    Article  CAS  PubMed  Google Scholar 

  7. Heneghan HM, Miller N, Kerin MJ. MiRNAs as biomarkers and therapeutic targets in cancer. Curr Opin Pharmacol. 2010;10:543–50.

    Article  CAS  PubMed  Google Scholar 

  8. Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012;81:145–66.

    Article  CAS  PubMed  Google Scholar 

  9. Zhang H, Chen Z, Wang X, Huang Z, He Z, Chen Y. Long non-coding RNA: a new player in cancer. J Hematol Oncol. 2013;6:37.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 2011;71:6320–6.

    Article  CAS  PubMed  Google Scholar 

  11. Yang Z, Zhou L, Wu LM, Lai MC, Xie HY, Zhang F, et al. Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol. 2011;18:1243–50.

    Article  PubMed  Google Scholar 

  12. Lu L, Zhu G, Zhang C, Deng Q, Katsaros D, Mayne ST, et al. Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer. Breast Cancer Res Treat. 2012;136:875–83.

    Article  CAS  PubMed  Google Scholar 

  13. Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, et al. HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene. 2013;32:1616–25.

    Article  CAS  PubMed  Google Scholar 

  14. Nakagawa T, Endo H, Yokoyama M, Abe J, Tamai K, Tanaka N, et al. Large noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free survival in human non-small cell lung cancer. Biochem Biophys Res Commun. 2013;436:319–24.

    Article  CAS  PubMed  Google Scholar 

  15. Li D, Feng J, Wu T, Wang Y, Sun Y, Ren J, et al. Long intergenic noncoding RNA HOTAIR is overexpressed and regulates PTEN methylation in laryngeal squamous cell carcinoma. Am J Pathol. 2013;182:64–70.

    Article  CAS  PubMed  Google Scholar 

  16. Nie Y, Liu X, Qu S, 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.

    Article  CAS  PubMed  Google Scholar 

  17. Lv XB, Lian GY, Wang HR, Song E, Yao H, Wang MH. Long noncoding RNA HOTAIR is a prognostic marker for esophageal squamous cell carcinoma progression and survival. PLoS One. 2013;8:e63516.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhang X, Zhou L, Fu G, Sun F, Shi J, Wei J, et al. The identification of an ESCC susceptibility SNP rs920778 that regulates the expression of lncRNA HOTAIR via a novel intronic enhancer. Carcinogenesis. 2014;35:2062–7.

    Article  CAS  PubMed  Google Scholar 

  19. Siewert JR, Stein HJ. Classification of adenocarcinoma of the oesophagogastric junction. Br J Surg. 1998;85:1457–9.

    Article  CAS  PubMed  Google Scholar 

  20. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. de Bakker PI, Burtt NP, Graham RR, Guiducci C, Yelensky R, Drake JA, et al. Transferability of tag SNPs in genetic association studies in multiple populations. Nat Genet. 2006;38:1298–303.

    Article  PubMed  Google Scholar 

  22. Yang M, Xie W, Mostaghel E, Nakabayashi M, Werner L, Sun T, et al. SLCO2B1 and SLCO1B3 may determine time to progression for patients receiving androgen deprivation therapy for prostate cancer. J Clin Oncol. 2011;29:2565–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001;25:402–8.

    Article  CAS  PubMed  Google Scholar 

  24. Beckedorff FC, Amaral MS, Deocesano-Pereira C, Verjovski-Almeida S. Long non-coding RNAs and their implications in cancer epigenetics. Biosci Rep. 2013;33:e00061.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Maruyama R, Suzuki H. Long noncoding RNA involvement in cancer. BMB Rep. 2012;45:604–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromation state to promote cancer metastasis. Nature. 2010;464:1071–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tang L, Zhang W, Su B, Yu B. Long noncoding RNA HOTAIR is associated with motility, invasion, and metastatic potential of metastatic melanoma. Biomed Res Int. 2013;2013:251098.

    PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We thank the cases and control individuals for taking part in this study. This research was supported by the National Natural Science Foundation (No. 81472335).

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Authors and Affiliations

  1. Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China

    Wei Guo, Zhiming Dong, Yanli Guo, Supeng Shen & Gang Kuang

  2. Department of Internal Medicine, The Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang, 050011, Hebei, China

    Yaling Bai & Jinsheng Xu

Authors
  1. Wei Guo
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  2. Zhiming Dong
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  3. Yaling Bai
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  4. Yanli Guo
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  5. Supeng Shen
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  6. Gang Kuang
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  7. Jinsheng Xu
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Corresponding author

Correspondence to Jinsheng Xu.

Additional information

Wei Guo and Zhiming Dong contributed equally to this work.

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Guo, W., Dong, Z., Bai, Y. et al. Associations between polymorphisms of HOTAIR and risk of gastric cardia adenocarcinoma in a population of north China. Tumor Biol. 36, 2845–2854 (2015). https://doi.org/10.1007/s13277-014-2912-y

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  • DOI: https://doi.org/10.1007/s13277-014-2912-y

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