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Tumor Biology

, Volume 36, Issue 9, pp 7159–7166 | Cite as

Overexpression of YB1 and EZH2 are associated with cancer metastasis and poor prognosis in renal cell carcinomas

  • Yong Wang
  • Yajing Chen
  • Hua Geng
  • Can Qi
  • Yunde Liu
  • Dan Yue
Research Article

Abstract

Renal cell carcinoma (RCC) is the most common type of kidney cancers in adults, and metastasis represents the major cause of mortality of RCC patients. The Y-box binding protein 1 (YB1) is a multifunctional oncoprotein in various malignancies. Enhancer of zeste homolog 2 (EZH2), a polycomb histone methyltransferase, is a key epigenetic modifier implicated in various cancer metastasis. However, the expression patterns and clinical correlations of both YB1 and EZH2 in RCC remain largely unclear. In this study, the expression of YB1 and EZH2 were examined using immunohistochemistry staining in a study cohort including 165 RCC and 80 tumor adjacent normal tissues. RCC tissues showed a significant higher nuclear expression of YB1 (p < 0.001) and EZH2 (p < 0.001) as compared with the normal counterparts. In addition, YB1 and EZH2 nuclear overexpression were found to be positively associated with RCC stage (p < 0.001 and p = 0.005), Fuhrman tumor grade (p = 0.022 and p = 0.044), and metastasis (p < 0.001 and p = 0.009). Overall survival analysis indicated patients with YB1 (p = 0.004, HR 5.656 (2.006–10.944)) and/or EZH2 (p = 0.006, HR 4.551 (2.124–9.438)) nuclear overexpression correlated with poor survival. More interestingly, YB1 and EZH2 nuclear expression was correlated (p = 0.005). Further studies demonstrated that EZH2 expression was significantly downregulated in YB1 knockdown RCC cell lines. Functionally, YB1 knockdown inhibited RCC invasion in vitro. In conclusion, YB1 and EZH2 expression was correlated and associated with RCC incidence, tumor stage, grade, metastasis, and survival.

Keywords

Enhancer of zeste homolog 2 Nuclear expression Renal cell carcinoma Y-Box-binding protein 1 

Notes

Acknowledgments

This work was supported by grants (81202380, 81402094, and 81202100) from the National Natural Science Foundation of China, grants (20111202120016) from Ph.D. Programs Foundation of Ministry of Education of China, grants (12JCQNJC07800, 12JCYBJC15600, and 14JCQNJC11600) from Natural Science Foundation of Tianjin, grant (2013M541189) from China Postdoctoral Science Foundation, and grant (201310062002) Tianjin national undergraduate training programs for innovation and entrepreneurship.

Conflicts of interest

None

Supplementary material

13277_2015_3417_MOESM1_ESM.docx (202 kb)
ESM 1 (DOCX 202 kb)

References

  1. 1.
    Vogelzang NJ, Stadler WM. Kidney cancer. Lancet. 1998;352:1691–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Singer EA, Gupta GN, Marchalik D, Srinivasan R. Evolving therapeutic targets in renal cell carcinoma. Curr Opin Oncol. 2013;25(3):273–80.PubMedGoogle Scholar
  3. 3.
    Wolffe AP, Tafuri S, Ranjan M, Familari M. The Y-box factors: a family of nucleic acid binding proteins conserved from Escherichia coli to man. New Biol. 1992;4(4):290–8.PubMedGoogle Scholar
  4. 4.
    Lasham A, Print CG, Woolley AG, Dunn SE, Braithwaite AW. YB-1: oncoprotein, prognostic marker and therapeutic target? Biochem J. 2013;449(1):11–23.CrossRefPubMedGoogle Scholar
  5. 5.
    Eliseeva IA, Kim ER, Guryanov SG, Ovchinnikov LP, Lyabin DN. Y-box-binding protein 1 (YB-1) and its functions. Biochemistry (Mosc). 2011;76(13):1402–33.CrossRefGoogle Scholar
  6. 6.
    Fushimi F, Taguchi K, Izumi H, Kohno K, Kuwano M, Ono M, et al. Peroxiredoxins, thioredoxin, and Y-box-binding protein-1 are involved in the pathogenesis and progression of dialysis-associated renal cell carcinoma. Virchows Arch. 2013;463(4):553–62.CrossRefPubMedGoogle Scholar
  7. 7.
    Shiota M, Takeuchi A, Song Y, Yokomizo A, Kashiwagi E, Uchiumi T, et al. Y-box binding protein-1 promotes castration-resistant prostate cancer growth via androgen receptor expression. Endocr Relat Cancer. 2011;18(4):505–17.CrossRefPubMedGoogle Scholar
  8. 8.
    Maciejczyk A, Szelachowska J, Ekiert M, Matkowski R, Hałoń A, Lage H, et al. Elevated nuclear YB1 expression is associated with poor survival of patients with early breast cancer. Anticancer Res. 2012;32(8):3177–84.PubMedGoogle Scholar
  9. 9.
    Song YH, Shiota M, Yokomizo A, Uchiumi T, Kiyoshima K, Kuroiwa K, et al. Twist1 and Y-box-binding protein-1 are potential prognostic factors in bladder cancer. Urol Oncol. 2013 Feb 6. pii: S1078-1439(12)00396-1.Google Scholar
  10. 10.
    Stratford AL, Habibi G, Astanehe A, Jiang H, Hu K, Park E, et al. Epidermal growth factor receptor (EGFR) is transcriptionally induced by the Y-box binding protein-1 (YB-1) and can be inhibited with Iressa in basal-like breast cancer, providing a potential target for therapy. Breast Cancer Res. 2007;9(5):R61.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Chattopadhyay R, Das S, Maiti AK, Boldogh I, Xie J, Hazra TK, et al. Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-1-mediated activation of the multidrug resistance gene MDR1. Mol Cell Biol. 2008;28(23):7066–80.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Jenuwein T, Allis CD. Translating the histone code. Science. 2001;293:1074.CrossRefPubMedGoogle Scholar
  13. 13.
    Muller J, Hart CM, Francis NJ, et al. Histone methyltransferase activity of a Drosophila polycomb group repressor complex. Cell. 2002;111:197.CrossRefPubMedGoogle Scholar
  14. 14.
    Varambally S, Dhanasekaran SM, Zhou M, et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature. 2002;419(6907):624–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Bachmann IM, Halvorsen OJ, Collett K, et al. EZH2 expression is associated with high proliferation rate and aggressive tumor subgroups in cutaneous melanoma and cancers of the endometrium, prostate, and breast. J Clin Oncol. 2006;24(2):268–73.CrossRefPubMedGoogle Scholar
  16. 16.
    Cai MY, Tong ZT, Zheng F, et al. EZH2 protein: a promising immunomarker for the detection of hepatocellular carcinomas in liver needle biopsies. Gut. 2011;60(7):967–76.CrossRefPubMedGoogle Scholar
  17. 17.
    Hinz S, Kempkensteffen C, Christoph F, et al. Expression of the polycomb group protein EZH2 and its relation to outcome in patients with urothelial carcinoma of the bladder. J Cancer Res Clin Oncol. 2008;134(3):331–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Hinz S, Weikert S, Magheli A, et al. Expression profile of the polycomb group protein enhancer of Zeste homologue 2 and its prognostic relevance in renal cell carcinoma. J Urol. 2009;182(6):2920–5.CrossRefPubMedGoogle Scholar
  19. 19.
    Wagener N, Holland D, Bulkescher J, et al. The enhancer of zeste homolog 2 gene contributes to cell proliferation and apoptosis resistance in renal cell carcinoma cells. Int J Cancer. 2008;123(7):1545–50.CrossRefPubMedGoogle Scholar
  20. 20.
    Wagener N, Macher-Goeppinger S, Pritsch M, et al. Enhancer of zeste homolog 2 (EZH2) expression is an independent prognostic factor in renal cell carcinoma. BMC Cancer. 2010;10:524.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Fujiwara-Okada Y, Matsumoto Y, Fukushi J, Setsu N, Matsuura S, Kamura S, et al. Y-box binding protein-1 regulates cell proliferation and is associated with clinical outcomes of osteosarcoma. Br J Cancer. 2013;108(4):836–47.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Wu K, Chen K, Wang C, Jiao X, Wang L, Zhou J, et al. Cell fate factor DACH1 represses YB-1-mediated oncogenic transcription and translation. Cancer Res. 2014;74(3):829–39.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Yong Wang
    • 1
  • Yajing Chen
    • 2
  • Hua Geng
    • 3
  • Can Qi
    • 4
  • Yunde Liu
    • 2
  • Dan Yue
    • 2
  1. 1.Department of Urology, Tianjin Institute of UrologyTianjin Medical University Second HospitalTianjinChina
  2. 2.School of Laboratory MedicineTianjin Medical UniversityTianjinChina
  3. 3.Research Center of Basic Medical SciencesTianjin Medical UniversityTianjinChina
  4. 4.Department of UrologyChildren’s Hospital of Hebei ProvinceShijiazhuangChina

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