Skip to main content

Advertisement

SpringerLink
Log in

High TUG1 expression is associated with chemotherapy resistance and poor prognosis in esophageal squamous cell carcinoma

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Long noncoding RNAs (lncRNAs) play critical roles in diverse biological processes such as tumorigenesis and metastasis. Taurine upregulated gene 1 (TUG1) is a cancer-related lncRNA that is associated with chromatin-modifying complexes and plays an important role in gene regulation. In this study, we determined the expression patterns of TUG1 in esophageal squamous cell carcinoma (ESCC) and evaluated its clinical significance.

Methods

The expression level of TUG1 was examined in 218 pairs of ESCC and adjacent non-cancerous tissues by using quantitative real-time polymerase chain reaction. The relationship between TUG1 expression and clinical features and prognosis was statistically analyzed.

Results

The expression level of TUG1 was significantly upregulated in ESCC tissues compared with paired adjacent normal tissues. High TUG1 expression was significantly correlated with chemotherapy resistance. Survival analysis showed that patients with high TUG1 expression had poor prognosis, especially for cases with well and moderate differentiation, ulcerative type, smaller size, and chemotherapy-sensitive tumors.

Conclusions

Our findings suggest that elevated TUG1 expression is related to chemotherapy resistance and may help predict a poor prognostic outcome of ESCC. TUG1 may provide a potential therapeutic target for ESCC.

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
Fig. 2

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65:5–29

    Article  PubMed  Google Scholar 

  2. Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J (2016) Cancer statistics in China, 2015. CA Cancer J Clin 66:115–132

    Article  PubMed  Google Scholar 

  3. Yang G, Lu X, Yuan L (2014) LncRNA: a link between RNA and cancer. Biochim Biophys Acta 1839:1097–1109

    Article  CAS  PubMed  Google Scholar 

  4. Matsushima K, Isomoto H, Yamaguchi N, Inoue N, Machida H, Nakayama T, Hayashi T, Kunizaki M, Hidaka S, Nagayasu T, Nakashima M, Ujifuku K, Mitsutake N, Ohtsuru A, Yamashita S, Korpal M, Kang Y, Gregory PA, Goodall GJ, Kohno S, Nakao K (2011) MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells. J Transl Med 9:30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wilusz JE, Sunwoo H, Spector DL (2009) Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 23:1494–1504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464:1071–1076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Raveh E, Matouk IJ, Gilon M, Hochberg A (2015) The H19 Long non-coding RNA in cancer initiation, progression and metastasis—a proposed unifying theory. Mol Cancer 14:184

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zhang L, Cao X, Zhang L, Zhang X, Sheng H, Tao K (2016) UCA1 overexpression predicts clinical outcome of patients with ovarian cancer receiving adjuvant chemotherapy. Cancer Chemother Pharmacol 77:629–634

    Article  CAS  PubMed  Google Scholar 

  9. Schmidt LH, Spieker T, Koschmieder S, Schaffers S, Humberg J, Jungen D, Bulk E, Hascher A, Wittmer D, Marra A, Hillejan L, Wiebe K, Berdel WE, Wiewrodt R, Muller-Tidow C (2011) 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 6:1984–1992

    Article  PubMed  Google Scholar 

  10. Sun J, Ding C, Yang Z, Liu T, Zhang X, Zhao C, Wang J (2016) The long non-coding RNA TUG1 indicates a poor prognosis for colorectal cancer and promotes metastasis by affecting epithelial-mesenchymal transition. J Transl Med 14:42

    Article  PubMed  PubMed Central  Google Scholar 

  11. Zhang X, Xu Y, He C, Guo X, Zhang J, He C, Zhang L, Kong M, Chen B, Zhu C (2015) Elevated expression of CCAT2 is associated with poor prognosis in esophageal squamous cell carcinoma. J Surg Oncol 111:834–839

    Article  CAS  PubMed  Google Scholar 

  12. Young TL, Matsuda T, Cepko CL (2005) The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina. Curr Biol 15:501–512

    Article  CAS  PubMed  Google Scholar 

  13. Huang MD, Chen WM, Qi FZ, Sun M, Xu TP, Ma P, Shu YQ (2015) Long non-coding RNA TUG1 is up-regulated in hepatocellular carcinoma and promotes cell growth and apoptosis by epigenetically silencing of KLF2. Mol Cancer 14:165

    Article  PubMed  PubMed Central  Google Scholar 

  14. Han Y, Liu Y, Gui Y, Cai Z (2013) Long intergenic non-coding RNA TUG1 is overexpressed in urothelial carcinoma of the bladder. J Surg Oncol 107:555–559

    Article  CAS  PubMed  Google Scholar 

  15. Ma B, Li M, Zhang L, Huang M, Lei JB, Fu GH, Liu CX, Lai QW, Chen QQ, Wang YL (2016) Upregulation of long non-coding RNA TUG1 correlates with poor prognosis and disease status in osteosarcoma. Tumour Biol 37:4445–4455

    Article  CAS  PubMed  Google Scholar 

  16. Li J, Zhang M, An G, Ma Q (2016) LncRNA TUG1 acts as a tumor suppressor in human glioma by promoting cell apoptosis. Exp Biol Med (Maywood) 241(6):644–649. doi:10.1177/1535370215622708

    Article  Google Scholar 

  17. Zhang EB, Yin DD, Sun M, Kong R, Liu XH, You LH, Han L, Xia R, Wang KM, Yang JS, De W, Shu YQ, Wang ZX (2014) P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression. Cell Death Dis 5:e1243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247

    Article  CAS  PubMed  Google Scholar 

  19. Qi P, Du X (2013) The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine. Mod Pathol 26:155–165

    Article  CAS  PubMed  Google Scholar 

  20. Lalevee S, Feil R (2015) Long noncoding RNAs in human disease: emerging mechanisms and therapeutic strategies. Epigenomics 7:877–879

    Article  CAS  PubMed  Google Scholar 

  21. Bhan A, Mandal SS (2014) Long noncoding RNAs: emerging stars in gene regulation, epigenetics and human disease. ChemMedChem 9:1932–1956

    Article  CAS  PubMed  Google Scholar 

  22. Li X, Wu Z, Mei Q, Li X, Guo M, Fu X, Han W (2013) Long non-coding RNA HOTAIR, a driver of malignancy, predicts negative prognosis and exhibits oncogenic activity in oesophageal squamous cell carcinoma. Br J Cancer 109:2266–2278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wang CM, Wu QQ, Li SQ, Chen FJ, Tuo L, Xie HW, Tong YS, Ji L, Zhou GZ, Cao G, Wu M, Lv J, Shi WH, Cao XF (2014) Upregulation of the long non-coding RNA PlncRNA-1 promotes esophageal squamous carcinoma cell proliferation and correlates with advanced clinical stage. Dig Dis Sci 59:591–597

    Article  CAS  PubMed  Google Scholar 

  24. Yang X, Song JH, Cheng Y, Wu W, Bhagat T, Yu Y, Abraham JM, Ibrahim S, Ravich W, Roland BC, Khashab M, Singh VK, Shin EJ, Yang X, Verma AK, Meltzer SJ, Mori Y (2014) Long non-coding RNA HNF1A-AS1 regulates proliferation and migration in oesophageal adenocarcinoma cells. Gut 63:881–890

    Article  CAS  PubMed  Google Scholar 

  25. Xu Y, Wang J, Qiu M, Xu L, Li M, Jiang F, Yin R, Xu L (2015) Upregulation of the long noncoding RNA TUG1 promotes proliferation and migration of esophageal squamous cell carcinoma. Tumour Biol 36:1643–1651

    Article  CAS  PubMed  Google Scholar 

  26. Xu TP, Liu XX, Xia R, Yin L, Kong R, Chen WM, Huang MD, Shu YQ (2015) SP1-induced upregulation of the long noncoding RNA TINCR regulates cell proliferation and apoptosis by affecting KLF2 mRNA stability in gastric cancer. Oncogene 34:5648–5661

    Article  CAS  PubMed  Google Scholar 

  27. Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL (2010) A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142:409–419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458:223–227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Liao WT, Jiang D, Yuan J, Cui YM, Shi XW, Chen CM, Bian XW, Deng YJ, Ding YQ (2011) HOXB7 as a prognostic factor and mediator of colorectal cancer progression. Clin Cancer Res 17:3569–3578

    Article  CAS  PubMed  Google Scholar 

  30. Koti M, Gooding RJ, Nuin P, Haslehurst A, Crane C, Weberpals J, Childs T, Bryson P, Dharsee M, Evans K, Feilotter HE, Park PC, Squire JA (2013) Identification of the IGF1/PI3 K/NF kappaB/ERK gene signalling networks associated with chemotherapy resistance and treatment response in high-grade serous epithelial ovarian cancer. BMC Cancer 13:549

    Article  PubMed  PubMed Central  Google Scholar 

  31. Tan J, Qiu K, Li M, Liang Y (2015) Double-negative feedback loop between long non-coding RNA TUG1 and miR-145 promotes epithelial to mesenchymal transition and radioresistance in human bladder cancer cells. FEBS Lett 589:3175–3181

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by Taizhou Society Development Project, Jiangsu, China (Grant No. TS201532); the 333 Project of Scientific Research Project Foundation, Jiangsu, China (Grant No. BRA2015224); and the 12th five-year plan Key Project of Science and Technology, China (Grant No. 2013ZX10002007).

Author information

Author notes

    Authors and Affiliations

    1. Department of Anesthesiology, Taizhou People’s Hospital, Taizhou, Jiangsu, China

      Lin Jiang, Canlin Sun & Zhenqin Ren

    2. Department of Pathology, Yangzhou University School of Medicine, Yangzhou, Jiangsu, China

      Wenchao Wang & Guoli Li

    3. Shanghai Engineering Center for Molecular Medicine, National Engineering Center for Biochip at Shanghai, Shanghai, China

      Haihui Sheng & Hengjun Gao

    4. Department of Pathology, Ruijing Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 00032, China

      Chaofu Wang

    5. Department of Pathology, Taizhou People’s Hospital, Taizhou, 225300, Jiangsu, China

      Hong Yu

    Authors
    1. Lin Jiang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Wenchao Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Guoli Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Canlin Sun
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Zhenqin Ren
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Haihui Sheng
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Hengjun Gao
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Chaofu Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Hong Yu
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Chaofu Wang or Hong Yu.

    Ethics declarations

    Conflict of interest

    All authors declare no conflict of interests.

    Additional information

    Lin Jiang and Wenchao Wang have contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Jiang, L., Wang, W., Li, G. et al. High TUG1 expression is associated with chemotherapy resistance and poor prognosis in esophageal squamous cell carcinoma. Cancer Chemother Pharmacol 78, 333–339 (2016). https://doi.org/10.1007/s00280-016-3066-y

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00280-016-3066-y

    Keywords

    Search

    Navigation