Skip to main content

Advertisement

SpringerLink
Log in

Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response

  • Original Article
  • Published:
Tumor Biology

Abstract

Long non-coding RNAs (lncRNAs) play important roles in carcinogenesis and drug efficacy. Platinum-based chemotherapy is first-line treatment for lung cancer chemotherapy. In this study, we aimed to investigate the association of well-characterized lung cancer lncRNA genetic polymorphisms with the lung cancer susceptibility and platinum-based chemotherapy response. A total of 498 lung cancer patients and 213 healthy controls were recruited in the study. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Thirteen polymorphisms in HOXA distal transcript antisense RNA (HOTTIP), HOX transcript antisense intergenic RNA (HOTAIR), H19, CDKN2B antisense RNA 1 (ANRIL), colon cancer-associated transcript 2 (CCAT2), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and maternally expressed gene 3 (MEG3) genes were genotyped by allele-specific MALDI-TOF mass spectrometry. We found that patients with HOTTIP rs5883064 C allele or rs1859168 A allele had increased lung cancer risk (P = 0.01, P = 0.01, respectively). CCAT2 rs6983267 (P = 0.02, adenocarcinoma) and H19 rs2107425 (P = 0.02, age under 50 years) showed strong relationship with lung cancer susceptibility. CCAT2 rs6983267, H19 rs2839698, MALAT1 rs619586, and HOTAIR rs7958904 were associated with platinum-based chemotherapy response in dominant model ((P = 0.02, P = 0.04, P = 0.04, P = 0.01, respectively). ANRIL rs10120688 (P = 0.02, adenocarcinoma) and rs1333049 (P = 0.04, small-cell lung cancer), H19 rs2107425 (P = 0.02, small-cell lung cancer) and HOTAIR rs1899663 (P = 0.03, male; P = 0.03, smoker) were associated with response to platinum-based chemotherapy. HOTTIP, CCAT2, H19, HOTAIR, MALATI, ANRIL genetic polymorphisms were significantly associated with lung cancer susceptibility or platinum-based chemotherapy response. They may be potential clinical biomarkers to predict lung cancer risk and platinum-based chemotherapy response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Parkin D, Pisani P, Ferlay J. Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer. 1993;54:594–606.

    Article  CAS  PubMed  Google Scholar 

  2. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet‐Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108.

    Article  PubMed  Google Scholar 

  3. Chen W, Zheng R, Zeng H, Zhang S, He J. Annual report on status of cancer in china, 2011. Chin J Cancer Res. 2015;27:2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.

    Article  PubMed  Google Scholar 

  5. Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136:629–41.

    Article  CAS  PubMed  Google Scholar 

  6. Koziol MJ, Rinn JL. RNA traffic control of chromatin complexes. Curr Opin Genet Dev. 2010;20:142–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Okazaki Y, Furuno M, Kasukawa T, Adachi J, Bono H, Kondo S, et al. Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature. 2002;420:563–73.

    Article  PubMed  Google Scholar 

  8. Li XP, Yin JY, Wang Y, He H, Li X, Gong WJ, et al. The atp7b genetic polymorphisms predict clinical outcome to platinum-based chemotherapy in lung cancer patients. Tumor Biol. 2014;35:8259–65.

    Article  CAS  Google Scholar 

  9. Yin JY, Huang Q, Yang Y, Zhang JT, Zhong MZ, Zhou HH, et al. Characterization and analyses of multidrug resistance-associated protein 1 (mrp1/abcc1) polymorphisms in Chinese population. Pharmacogenet Genomics. 2009;19:206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci. 2009;106:9362–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Liu Y, Pan S, Liu L, Zhai X, Liu J, Wen J, et al. A genetic variant in long non-coding rna hulc contributes to risk of hbv-related hepatocellular carcinoma in a Chinese population. PLoS One. 2012;7:e35145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst. 2000;92:205–16.

    Article  CAS  PubMed  Google Scholar 

  13. Deng H, Chen L, Fan T, Zhang B, Xu Y, Geng Q. Long non-coding RNA hottip promotes tumor growth and inhibits cell apoptosis in lung cancer. Cell Mol Biol (Noisy-le-Grand France). 2014;61:34–40.

    Google Scholar 

  14. JiP D, Wang W. MALAT-1, a novel noncoding RNA, and thymosin β4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene. 2003;22:8031.

    Article  CAS  Google Scholar 

  15. Schmidt LH, Spieker T, Koschmieder S, Humberg J, Jungen D, Bulk E, et al. The long noncoding malat-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth. J Thorac Oncol. 2011;6:1984–92.

    Article  PubMed  Google Scholar 

  16. Lai MC, Yang Z, Zhou L, Zhu QQ, Xie HY, Zhang F, et al. Long non-coding RNA malat-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation. Med Oncol. 2012;29:1810–6.

    Article  CAS  PubMed  Google Scholar 

  17. Gabory A, Jammes H, Dandolo L. The h19 locus: role of an imprinted non-coding RNA in growth and development. Bioessays. 2010;32:473–80.

    Article  CAS  PubMed  Google Scholar 

  18. Kondo M, Suzuki H, Ueda R, Osada H, Takagi K, Takahashi T. Frequent loss of imprinting of the h19 gene is often associated with its overexpression in human lung cancers. Oncogene. 1995;10:1193–8.

    CAS  PubMed  Google Scholar 

  19. Barsyte-Lovejoy D, Lau SK, Boutros PC, Khosravi F, Jurisica I, Andrulis IL, et al. The c-myc oncogene directly induces the h19 noncoding RNA by allele-specific binding to potentiate tumorigenesis. Cancer Res. 2006;66:5330–7.

    Article  CAS  PubMed  Google Scholar 

  20. Tsang W, Kwok T. Riboregulator h19 induction of mdr1-associated drug resistance in human hepatocellular carcinoma cells. Oncogene. 2007;26:4877–81.

    Article  CAS  PubMed  Google Scholar 

  21. Verhaegh GW, Verkleij L, Vermeulen SH, den Heijer M, Witjes JA, Kiemeney LA. Polymorphisms in the h19 gene and the risk of bladder cancer. Eur Urol. 2008;54:1118–26.

    Article  CAS  PubMed  Google Scholar 

  22. Riaz M, Berns EM, Sieuwerts AM, Ruigrok-Ritstier K, de Weerd V, Groenewoud A, et al. Correlation of breast cancer susceptibility loci with patient characteristics, metastasis-free survival, and mRNA expression of the nearest genes. Breast Cancer Res Treat. 2012;133:843–51.

    Article  CAS  PubMed  Google Scholar 

  23. Yang C, Tang R, Ma X, Wang Y, Luo D, Xu Z, Zhu Y, Yang L. Tag SNPs in long non-coding RNA H19 contribute to susceptibility to gastric cancer in the Chinese Han population. Oncotarget 2015.

  24. Ling H, Spizzo R, Atlasi Y, Nicoloso M, Shimizu M, Redis RS, et al. Ccat2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. Genome Res. 2013;23:1446–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Qiu M, Xu Y, Yang X, Wang J, Hu J, Xu L, et al. Ccat2 is a lung adenocarcinoma-specific long non-coding RNA and promotes invasion of non-small cell lung cancer. Tumor Biol. 2014;35:5375–80.

    Article  CAS  Google Scholar 

  26. 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 

  27. Liu Z, Sun M, Lu K, Liu J, Zhang M, Wu W, et al. The long noncoding RNA hotair contributes to cisplatin resistance of human lung adenocarcinoma cells via downregulation of p21 (waf1/cip1) expression. PLoS One. 2013;8:e77293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Xue Y, Gu D, Ma G, Zhu L, Hua Q, Chu H, et al. Genetic variants in lncrna hotair are associated with risk of colorectal cancer. Mutagenesis. 2015;30:303–10.

    Article  CAS  PubMed  Google Scholar 

  29. Guo W, Dong Z, Bai Y, Guo Y, Shen S, Kuang G, et al. Associations between polymorphisms of hotair and risk of gastric cardia adenocarcinoma in a population of North China. Tumor Biol. 2015;36:2845–54.

    Article  CAS  Google Scholar 

  30. Nie FQ, Sun M, Yang JS, Xie M, Xu TP, Xia R, et al. Long noncoding RNA ANRIL promotes non–small cell lung cancer cell proliferation and inhibits apoptosis by silencing KLF2 and P21 expression. Mol Cancer Ther. 2015;14:268–77.

    Article  CAS  PubMed  Google Scholar 

  31. Yap KL, Li S, Muñoz-Cabello AM, Raguz S, Zeng L, Mujtaba S, et al. Molecular interplay of the noncoding RNA ANRIL and methylated histone h3 lysine 27 by polycomb cbx7 in transcriptional silencing of ink4a. Mol Cell. 2010;38:662–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yu W, Gius D, Onyango P, Muldoon-Jacobs K, Karp J, Feinberg AP, et al. Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature. 2008;451:202–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Yuan XW, Zhu XF, Huang XF, Sheng PY, He AS, Yang ZB, et al. P14arf sensitizes human osteosarcoma cells to cisplatin-induced apoptosis in a p53-independent manner. Cancer Biol Ther. 2007;6:1074–80.

    Article  CAS  PubMed  Google Scholar 

  34. Deng X, Kim M, Vandier D, Jung YJ, Rikiyama T, Sgagias MK, et al. Recombinant adenovirus-mediated p14 arf overexpression sensitizes human breast cancer cells to cisplatin. Biochem Biophys Res Commun. 2002;296:792–8.

    Article  CAS  PubMed  Google Scholar 

  35. Al-Mohanna MA, Manogaran PS, Al-Mukhalafi Z, Al-Hussein KA, Aboussekhra A. The tumor suppressor p16ink4a gene is a regulator of apoptosis induced by ultraviolet light and cisplatin. Oncogene. 2004;23:201–12.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank all the subjects volunteered to participate in this study. This work was supported by the National High-Tech R&D Program of China (863 Program) (2012AA02A517, 2012AA02A518) and National Natural Science Foundation of China (81173129, 81202595, 81373490, 81573508).

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, China

    Wei-Jing Gong, Ji-Ye Yin, Chao Fang, Di Xiao, Wei Zhang, Hong-Hao Zhou, Xi Li & Zhao-Qian Liu

  2. Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, 410078, China

    Wei-Jing Gong, Ji-Ye Yin, Chao Fang, Di Xiao, Wei Zhang, Hong-Hao Zhou, Xi Li & Zhao-Qian Liu

  3. Hunan Province Cooperation Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, China

    Wei-Jing Gong, Ji-Ye Yin, Chao Fang, Di Xiao, Wei Zhang, Hong-Hao Zhou, Xi Li & Zhao-Qian Liu

  4. Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, 410008, China

    Xiang-Ping Li

Authors
  1. Wei-Jing Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ji-Ye Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiang-Ping Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chao Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Di Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hong-Hao Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Zhao-Qian Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xi Li or Zhao-Qian Liu.

Ethics declarations

Conflicts of interest

None

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplement Table 1

(DOCX 16 kb)

Supplement Table 2

(DOCX 18 kb)

Supplement Table 3

(DOCX 19 kb)

Supplement Table 4

(DOCX 18 kb)

Supplement Figure 1

(DOCX 77 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gong, WJ., Yin, JY., Li, XP. et al. Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response. Tumor Biol. 37, 8349–8358 (2016). https://doi.org/10.1007/s13277-015-4497-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-4497-5

Keywords

Search

Navigation