Tumor Biology

, Volume 36, Issue 3, pp 1643–1651 | Cite as

Upregulation of the long noncoding RNA TUG1 promotes proliferation and migration of esophageal squamous cell carcinoma

  • Youtao Xu
  • Jie Wang
  • Mantang Qiu
  • Lei Xu
  • Ming Li
  • Feng Jiang
  • Rong Yin
  • Lin Xu
Research Article


Esophageal squamous cell carcinoma (ESCC) is one of the prevalent and deadly cancers worldwide, especially in Eastern Asia. The prognosis of ESCC remains poor; thus, it is still necessary to further dissect the underlying mechanisms and explore therapeutic targets of ESCC. Recent studies show that long noncoding RNAs (lncRNAs) have critical roles in diverse biological processes, including tumorigenesis. Some lncRNAs, such as HOTAIR and POU3F3, were reported to play important roles in ESCC. Here, we characterized the expression profile of taurine-upregulated gene 1 (TUG1), a lncRNA recruiting and binding to polycomb repressive complex 2 (PRC2), in ESCC. In a cohort of 62 patients, TUG1 was significantly overexpressed in ESCC tissues compared with paired adjacent normal tissues, and high expression level of TUG1 was associated with family history and upper segment of esophageal cancer (p < 0.05). Further, in vitro silencing TUG1 via siRNA inhibited the proliferation and migration of ESCC cells and blocked the progression of cell cycle. Therefore, our study indicates that TUG1 promotes proliferation and migration of ESCC cells and is a potential oncogene of ESCC.


TUG1 Long noncoding RNA Esophageal squamous cell carcinoma Expression 


Conflicts of interest


Funding sources

This study is funded by the Natural Science Foundation of China (81372321 to L. Xu; 81201830 and 81472200 to R. Yin), Natural Science Foundation for High Education of Jiangsu Province (13KJB320010 to R. Yin), Foundation of Jiangsu Cancer Hospital (ZQ201103 to J. Wang), and Jiangsu Provincial Special Program of Medical Science (BL2012030 to L. Xu).

Supplementary material

13277_2014_2763_Fig6_ESM.gif (118 kb)
Figure S1

Apotosis assay of ECSS cells. TE-13 and KYSE-410 cells transfected with si-NC (siRNA negative control) or si-TUG1 (siRNA specific to TUG1). Thirty-six hours after transfection, cells were analyzed by flow cytometry. (GIF 117 kb)

13277_2014_2763_MOESM1_ESM.tif (239 kb)
High Resolution Image (TIFF 238 kb)


  1. 1.
    Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.CrossRefPubMedGoogle Scholar
  2. 2.
    Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349:2241–52.CrossRefPubMedGoogle Scholar
  3. 3.
    Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005;97:142–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Matsushima K, Isomoto H, Yamaguchi N, Inoue N, Machida H, Nakayama T, et al. 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. 2011;9:30.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Isono K, Sato H, Nakayama K. Results of a nationwide study on the three-field lymph node dissection of esophageal cancer. Oncology. 1991;48:411–20.CrossRefPubMedGoogle Scholar
  6. 6.
    McCann J. Esophageal cancers: changing character, increasing incidence. J Natl Cancer Inst. 1999;91:497–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12:861–74.CrossRefPubMedGoogle Scholar
  8. 8.
    Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011;43:904–14.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    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. Tumour Biol : J Int Soc Oncodevelopmental Biol Med. 2014;35:5375–80.CrossRefGoogle Scholar
  10. 10.
    Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK, Munson G, et al. LincRNAs act in the circuitry controlling pluripotency and differentiation. Nature. 2011;477:295–300.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science. 2010;329:689–93.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Qiu MT, Hu JW, Yin R, Xu L. Long noncoding RNA: an emerging paradigm of cancer research. Tumour Biol : J Int Soc Oncodevelopmental Biol Med. 2013;34:613–20.CrossRefGoogle Scholar
  13. 13.
    Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464:1071–6.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Tano K, Mizuno R, Okada T, Rakwal R, Shibato J, Masuo Y, et al. Malat-1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility-related genes. FEBS Lett. 2010;584:4575–80.CrossRefPubMedGoogle Scholar
  15. 15.
    Geng YJ, Xie SL, Li Q, Ma J, Wang GY. Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J Int Med Res. 2011;39:2119–28.CrossRefPubMedGoogle Scholar
  16. 16.
    Ren S, Wang F, Shen J, Sun Y, Xu W, Lu J, et al. Long non-coding RNA metastasis associated in lung adenocarcinoma transcript 1 derived miniRNA as a novel plasma-based biomarker for diagnosing prostate cancer. Eur J Cancer. 2013;49:2949–59.CrossRefPubMedGoogle Scholar
  17. 17.
    Schmidt LH, Spieker T, Koschmieder S, Schaffers S, Humberg J, Jungen D, 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 : Off Publ Int Assoc Stud Lung Cancer. 2011;6:1984–92.CrossRefGoogle Scholar
  18. 18.
    Young TL, Matsuda T, Cepko CL. The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina. Curr Biol : CB. 2005;15:501–12.CrossRefPubMedGoogle Scholar
  19. 19.
    Zhang Q, Geng PL, Yin P, Wang XL, Jia JP, Yao J. Down-regulation of long non-coding RNA TUG1 inhibits osteosarcoma cell proliferation and promotes apoptosis. Asian Pac J Cancer Prev : APJCP. 2013;14:2311–5.CrossRefPubMedGoogle Scholar
  20. 20.
    Han Y, Liu Y, Gui Y, Cai Z. Long intergenic non-coding RNA TUG1 is overexpressed in urothelial carcinoma of the bladder. J Surg Oncol. 2013;107:555–9.CrossRefPubMedGoogle Scholar
  21. 21.
    Zhang EB, Yin DD, Sun M, Kong R, Liu XH, You LH, et al. 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. 2014;5:e1243.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    VanGuilder HD, Vrana KE, Freeman WM. Twenty-five years of quantitative PCR for gene expression analysis. BioTech. 2008;44:619–26.CrossRefGoogle Scholar
  23. 23.
    Qi P, Du X. The long non-coding RNAs, a new cancer diagnostic and therapeutic gold mine. Mod Pathol : Off J US Can Acad Pathol, Inc. 2013;26:155–65.CrossRefGoogle Scholar
  24. 24.
    Ma L, Bajic VB, Zhang Z. On the classification of long non-coding RNAs. RNA Biol. 2013;10:925–33.PubMedGoogle Scholar
  25. 25.
    Wilusz JE, Sunwoo H, Spector DL. Long noncoding RNAs: functional surprises from the RNA world. Genes Dev. 2009;23:1494–504.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Li J, Xuan Z, Liu C. Long non-coding RNAs and complex human diseases. Int J Mol Sci. 2013;14:18790–808.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    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.CrossRefPubMedGoogle Scholar
  28. 28.
    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.CrossRefPubMedGoogle Scholar
  29. 29.
    Hao JJ, Gong T, Zhang Y, Shi ZZ, Xu X, Dong JT, et al. Characterization of gene rearrangements resulted from genomic structural aberrations in human esophageal squamous cell carcinoma KYSE150 cells. Gene. 2013;513:196–201.CrossRefPubMedGoogle Scholar
  30. 30.
    Li W, Zheng J, Deng J, You Y, Wu H, Li N, et al. Increased levels of the long intergenic non-protein coding RNA POU3F3 promote DNA methylation in esophageal squamous cell carcinoma cells. Gastroenterology. 2014;146:1714–26. e1715.CrossRefPubMedGoogle Scholar
  31. 31.
    Yang X, Song JH, Cheng Y, Wu W, Bhagat T, Yu Y, et al. Long non-coding RNA HNF1A-AS1 regulates proliferation and migration in oesophageal adenocarcinoma cells. Gut. 2014;63:881–90.CrossRefPubMedGoogle Scholar
  32. 32.
    Wang CM, Wu QQ, Li SQ, Chen FJ, Tuo L, Xie HW, et al. Upregulation of the long non-coding RNA PlncRNA-1 promotes esophageal squamous carcinoma cell proliferation and correlates with advanced clinical stage. Dig Dis Sci. 2014;59:591–7.CrossRefPubMedGoogle Scholar
  33. 33.
    Li X, Wu Z, Mei Q, Li X, Guo M, Fu X, et al. Long non-coding RNA HOTAIR, a driver of malignancy, predicts negative prognosis and exhibits oncogenic activity in oesophageal squamous cell carcinoma. Br J Cancer. 2013;109:2266–78.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Gao Y, Hu N, Han X, Giffen C, Ding T, Goldstein A, et al. Family history of cancer and risk for esophageal and gastric cancer in Shanxi, China. BMC Cancer. 2009;9:269.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Guo W, Blot WJ, Li JY, Taylor PR, Liu BQ, Wang W, et al. A nested case-control study of oesophageal and stomach cancers in the Linxian nutrition intervention trial. Int J Epidemiol. 1994;23:444–50.CrossRefPubMedGoogle Scholar
  36. 36.
    Mahboubi E, Kmet J, Cook PJ, Day NE, Ghadirian P, Salmasizadeh S. Oesophageal cancer studies in the Caspian littoral of Iran: the Caspian cancer registry. Br J Cancer. 1973;28:197–214.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Vigneswaran WT, Trastek VF, Pairolero PC, Deschamps C, Daly RC, Allen MS. Extended esophagectomy in the management of carcinoma of the upper thoracic esophagus. J Thorac Cardiovasc Surg. 1994;107:901–6. discussion 906–907.PubMedGoogle Scholar
  38. 38.
    EL Andaloussi S, Mager I, Breakefield XO, Wood MJ. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013;12:347–57.CrossRefPubMedGoogle Scholar
  39. 39.
    Gezer U, Ozgur E, Cetinkaya M, Isin M, Dalay N: Long non-coding RNAs with low expression levels in cells are enriched in secreted exosomes. Cell biology international 2014.Google Scholar
  40. 40.
    Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A. 2009;106:11667–72.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Yamaguchi H, Hung MC. Regulation and role of EZH2 in cancer. Cancer Res Treat : Off J Korean Cancer Assoc. 2014;46:209–22.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer ResearchCancer Institute of Jiangsu ProvinceNanjingPeople’s Republic of China
  2. 2.The First Clinical College of Nanjing Medical UniversityNanjingChina
  3. 3.Department of Scientific Research, Affiliated Cancer Hospital, Cancer Institute of Jiangsu ProvinceNanjing Medical UniversityNanjingChina
  4. 4.The Fourth Clinical College of Nanjing Medical UniversityNanjingChina
  5. 5.Department of Thoracic Surgery, The Affiliated Nanjing Hospital of Nanjing Medical UniversityNanjingChina

Personalised recommendations