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Medical Oncology

, 31:64 | Cite as

URG11 predicts poor prognosis of pancreatic cancer by enhancing epithelial–mesenchymal transition-driven invasion

  • Wei Peng
  • Jun Zhang
  • Jie LiuEmail author
Original Paper

Abstract

The poor prognosis and high recurrent rate of pancreatic cancer (PC) necessitates the discovery of new predictive markers of PC invasion and prognosis. In this study, we evaluated the expression pattern of up-regulated gene 11 (URG11) in a tissue microarray with 18 pairs of PC and adjacent normal tissues. It was shown that URG11 was significantly up-regulated in PC tissues. High expression levels of URG11 were detected in all PC specimens, but were rarely detected in adjacent non-tumorous tissues. In addition, high expression of URG11 was correlated to poor prognosis. Furthermore, it was discovered that URG11 was correlated to epithelial–mesenchymal transition (EMT) markers and clinical pathological parameters indicative of high PC invasion, while knockdown of URG11 significantly changed the expression pattern of EMT markers and decreased the invasion of PC cells. These findings indicate that URG11 might enhance the invasion of PC by inducing EMT and thus lead to poor PC prognosis. Thus, URG11 has the potential to be a new predictive biomarker of PC invasion and prognosis, which may help in the diagnosis and treatment of PC patients.

Keywords

Up-regulated gene 11 Pancreatic cancer Prognosis Epithelial–mesenchymal transition Invasion 

Notes

Acknowledgments

This work was supported by Grants from the National Natural Science Foundation of China (Nos. 81125001, 91129702 and 81161120431) and the Ministry of Science and Technology of China (No. 2010CB732405).

Conflict of interest

The authors declare that they have no conflict of interests.

References

  1. 1.
    Wolfgang CL, Herman JM, Laheru DA, Klein AP, Erdek MA, Fishman EK, et al. Recent progress in pancreatic cancer. Cancer J Clin. 2013;63(5):318–48. doi: 10.3322/caac.21190.CrossRefGoogle Scholar
  2. 2.
    Hidalgo M. Pancreatic cancer. N Engl J Med. 2010;362(17):1605–17. doi: 10.1056/NEJMra0901557.PubMedCrossRefGoogle Scholar
  3. 3.
    Maitra A, Hruban RH. Pancreatic cancer. Annu Rev Pathol Mech Dis. 2008. 157–88.Google Scholar
  4. 4.
    Lian ZR, Liu J, Li L, Li X, Clayton MM, Wu MC, et al. Enhanced cell survival by the hepatitis B × antigen effector, URG11, is associated with up-regulation of beta-catenin. Clin Cancer Res. 2005;11(24):9160S–1S.Google Scholar
  5. 5.
    Zou X, Li XH, Liu J, Lian ZR, Fan R, Du R, et al. Preparation and characterization of a specific monoclonal antibody against a new gene product: URG11. Hybridoma. 2006;25(6):378–81. doi: 10.1089/hyb.2006.25.378.PubMedCrossRefGoogle Scholar
  6. 6.
    Liu J. MAb against new gene product URG11. Hybridoma. 2007;26(1):46–8. doi: 10.1089/hyb.2006.9999.1.CrossRefGoogle Scholar
  7. 7.
    Lian ZR, Liu J, Li L, Li XX, Clayton M, Wu MC, et al. Enhanced cell survival of Hep3B cells by the hepatitis B × antigen effector, URG11, is associated with upregulation of beta-catenin. Hepatology. 2006;43(3):415–24. doi: 10.1002/hep.21053.PubMedCrossRefGoogle Scholar
  8. 8.
    Du R, Xia L, Sun SR, Lian ZR, Zou X, Gao J, et al. URG11 promotes gastric cancer growth and invasion by activation of beta-catenin signalling pathway. J Cell Mol Med. 2010;14(3):621–35. doi: 10.1111/j.1582-4934.2008.00622.x.PubMedGoogle Scholar
  9. 9.
    Fan R, Li XH, Du WQ, Zou X, Du R, Zhao LN, et al. Adenoviral-mediated RNA interference targeting URG11 inhibits growth of human hepatocellular carcinoma. Int J Cancer. 2011;128(12):2980–93. doi: 10.1002/ijc.25624.PubMedCrossRefGoogle Scholar
  10. 10.
    Du R, Huang C, Bi Q, Zhai Y, Xia L, Liu J, et al. URG11 mediates hypoxia-induced epithelial-to-mesenchymal transition by modulation of E-cadherin and beta-catenin. Biochem Biophys Res Commun. 2010;391(1):135–41. doi: 10.1016/j.bbrc.2009.11.019.PubMedCrossRefGoogle Scholar
  11. 11.
    He L, Zhou X, Qu C, Hu L, Tang Y, Zhang Q, et al. Musashi2 predicts poor prognosis and invasion in hepatocellular carcinoma by driving epithelial–mesenchymal transition. J Cell Mol Med. 2014;18(1):49–58. doi: 10.1111/jcmm.12158.PubMedCrossRefGoogle Scholar
  12. 12.
    Du J, Wang JW, Tan G, Cai ZG, Zhang L, Tang B, et al. Aberrant elevated microRNA-146a in dendritic cells (DC) induced by human pancreatic cancer cell line BxPC-3-conditioned medium inhibits DC maturation and activation. Med Oncol. 2012;29(4):2814–23. doi: 10.1007/s12032-012-0175-2.PubMedCrossRefGoogle Scholar
  13. 13.
    Lee CL, He H, Jiang YJ, Di Y, Yang F, Li J, et al. Elevated expression of tumor miR-222 in pancreatic cancer is associated with Ki67 and poor prognosis. Med Oncol. 2013;30(4). doi: 10.1007/s12032-013-0700-y.
  14. 14.
    Gunturu KS, Yao XP, Cong XY, Thumar JR, Hochster HS, Stein SM, et al. FOLFIRINOX for locally advanced and metastatic pancreatic cancer: single institution retrospective review of efficacy and toxicity. Med Oncol. 2013;30(1). doi: 10.1007/s12032-012-0361-2.
  15. 15.
    Maheshwari V, Moser AJ. Current management of locally advanced pancreatic cancer. Nat Clin Pract Gastroenterol Hepatol. 2005;2(8):356–64. doi: 10.1038/ncpgasthep0240.PubMedCrossRefGoogle Scholar
  16. 16.
    Bapat AA, Hostetter G, Von Hoff DD, Han HY. Perineural invasion and associated pain in pancreatic cancer. Nat Rev Cancer. 2011;11(10):695–707. doi: 10.1038/nrc3131.PubMedCrossRefGoogle Scholar
  17. 17.
    Thiery JP. Epithelial–mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002;2(6):442–54. doi: 10.1038/nrc822.PubMedCrossRefGoogle Scholar
  18. 18.
    Zhao N, Sun BC, Zhao XL, Liu ZY, Sun T, Qiu ZQ, et al. Coexpression of Bcl-2 with epithelial–mesenchymal transition regulators is a prognostic indicator in hepatocellular carcinoma. Med Oncol. 2012;29(4):2780–92. doi: 10.1007/s12032-012-0207-y.PubMedCrossRefGoogle Scholar
  19. 19.
    Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial–mesenchymal transition. Nat Rev Mol Cell Biol. 2014;15(3):178–96. doi: 10.1038/nrm3758.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Digestive Diseases, Huashan HospitalFudan UniversityShanghaiChina
  2. 2.Institutes of Biomedical Sciences, Department of Immunology of Shanghai Medical SchoolFudan UniversityShanghaiChina

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