Skip to main content
Log in

Analysis of WWOX gene expression and protein levels in pterygium

  • Original Paper
  • Published:
International Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

Pterygium, a degenerative and hyperplastic lesion, has premalignant properties as a tumor analog. WWOX is a tumor suppressor gene and involved in many signal pathways, such as cell proliferation, embryonic development, metabolism and apoptosis. In many cancers, the loss of WWOX or the presence of abnormal transcripts indicates the tumor suppressor activity of WWOX. In this study, it was aimed to determine WWOX gene expression and protein levels in pterygium which may be a tumor analog.

Methods

For this purpose, the WWOX gene expression change in 27 pterygium tissue was investigated by real-time PCR method, and the change in WWOX protein was investigated using the Western blot method.

Results

According to our results, it was found that the expression and protein levels of WWOX gene in pterygium tissue decreased significantly compared to control tissue (p < 0.05).

Conclusion

This information indicates that a decrease in expression and protein level in pterygium tissue of WWOX, a tumor suppressor gene, supports claims that pterygium may be a cancer analog tissue.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Donald THT, Wen YT, Yan PL, Hak-Su G, Duncan RS (2000) Apoptosis and apoptosis related gene expression in normal conjunctiva and pterygium. Br J Ophthalmol 84:212–216

    Article  Google Scholar 

  2. Cárdenas-Cantú E, Zavala J, Valenzuela J, Valdez-García JE (2016) Molecular basis of pterygium development. Semin Ophthalmol 31(6):567–583

    PubMed  Google Scholar 

  3. Liu T, Liu Y, Xie L, He X, Ji Bai J (2013) Progress in the pathogenesis of pterygium. Curr Eye Res 38(12):1191–1197

    Article  CAS  PubMed  Google Scholar 

  4. Sebastiá R, Ventura MP, Solari HP, Antecka E, Orellana ME, Burnier MN (2013) Immunohistochemical detection of Hsp90 and Ki-67 in pterygium. Diagn Pathol 8:32

    Article  PubMed  PubMed Central  Google Scholar 

  5. Demiryürek S, Saracaloglu A, Kimyon S, Mete A, Eronat O, Temiz E, Nacarkahya G, Tunca ZS, Düzen B, Saygili O, Güngör K, Karakök M, Demiryürek AT (2019) Increased expressions of ICAM-2 and ICAM-3 in pterygium. Curr Eye Res. https://doi.org/10.1080/02713683.2019.1570527

    Article  PubMed  Google Scholar 

  6. Liang K, Jiang Z, Ding B, Cheng P, Huang D, Tao L (2011) Expression of cell proliferation and apoptosis biomarkers in pterygia and normal conjunctiva. Mol Vis 17:1687–1693

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Girolamo ND, Chui J, Coroneo MT, Wakefield D (2004) Pathogenesis of pterygia: role of cytokines, growth factors, and matrix metalloproteinases. Prog Retin Eye Res 23:195–228

    Article  PubMed  Google Scholar 

  8. Huang YH, Chang NS, Tseng SH (2015) Expression of WW domain-containing oxidoreductase WWOX in pterygium. Mol Vis 21:711–717

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Tung JN, Chiang CC, Tsai YY, Chou YY, Yeh KT, Lee H, Cheng YW (2010) CyclinD1 protein expressed in pterygia is associated with β-catenin protein localization. Mol Vis 16:2733–2738

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Baryła I, Styczen-Binkowska E, Bednarek AK (2015) Alteration of WWOX in human cancer, a clinical view. Exp Biol Med 240:305–314

    Article  Google Scholar 

  11. Schrock MS, Huebner K (2015) WWOX: a fragile tumor suppressor. Exp Biol Med 240:296–304

    Article  CAS  Google Scholar 

  12. Yang Z, Lan H, Chen X, Li P, Li S, Mo W, Tang A (2014) Molecular alterations of the WWOX gene in nasopharyngeal carcinoma. Neoplasma 61(2):170–176

    Article  CAS  PubMed  Google Scholar 

  13. Lin JT, Li HY, Chang NS, Lin CH, Chen YC, Lu PJ (2015) WWOX suppresses prostate cancer cell progression through cyclin D1-mediated cell cycle arrest in the G1 phase. Cell Cycle 14(3):408–416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative CT method. Nat Protoc 3(6):1101–1108

    Article  CAS  PubMed  Google Scholar 

  15. Adıguzel U, Karabacak T, Sarı A, Oz O, Cınel L (2007) Cyclooxygenase-2 expression in primary and recurrent pterygium. Eur J Ophthalmol 17(6):879–884

    Article  PubMed  Google Scholar 

  16. Spandidos DA, Sourvinos G, Kiaris H, Tsamparlakis J (1997) Microsatellite instability and loss of heterozygosity in human pterygia. Br J Ophthalmol 81:493–496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Weinstein O, Rosenthal G, Zirkin H, Monos T, Lifshitz T, Argov S (2002) Overexpression of p53 tumor suppressor gene in pterygia. Eye 16:619–621

    Article  CAS  PubMed  Google Scholar 

  18. Wistuba II, Behrens C, Virmani AK (2000) High resolution chromosome 3p allelotyping of human lung cancer and preneoplastic/preinvasive bronchial epithelium reveals multiple, discontinuous sites of 3p allele loss and three regions of frequent breakpoints. Cancer Res 60:1949–1960

    CAS  PubMed  Google Scholar 

  19. Nowakowska M, Płuciennik E, Wujcicka W, Sitkiewicz A, Kazanowska B, Zielińska E, Bednarek AK (2014) The correlation analysis of WWOX expression and cancer related genes in neuroblastoma—a real time RT-PCR study. Acta Biochim Pol 61(1):91–97

    Article  PubMed  Google Scholar 

  20. Abdeen SK, David UB, Shweiki A, Maly B, Aqeilan RI (2018) Somatic loss of WWOX is associated with TP53 perturbation in basal-like breast cancer. Cell Death Dis 9:832

    Article  PubMed  PubMed Central  Google Scholar 

  21. Aldaz CM, Ferguson BW, Abba MC (1846) WWOX at the crossroads of cancer, metabolic syndrome related traits and CNS pathologies. Biochim Biophys Acta 2014:188–200

    Google Scholar 

  22. Płuciennik E, Nowakowska M, Wujcicka WI, Sitkiewicz A, Kazanowska B, Zielińska E, Bednarek AK (2012) Genetic alterations of WWOX in Wilms’ tumor are involved in its carcinogenesis. Oncol Rep 28(4):1417–1422

    Article  PubMed  Google Scholar 

  23. Qin HR, Iliopoulos D, Nakamura T, Costinean S, Volinia S, Druck T, Sun J, Okumura H, Huebner K (2007) Wwox suppresses prostate cancer cell growth through modulation of ErbB2-mediated androgen receptor signaling. Mol Cancer Res 5(9):957–965

    Article  CAS  PubMed  Google Scholar 

  24. Yang J, Zhang W (2008) WWOX tumor suppressor gene. Histol Histopathol 23:877–882

    CAS  PubMed  Google Scholar 

  25. Nunez MI, Ludes-Meyers J, Abba MC, Kil H, Abbey NW, Page RE, Sahin A, Klein-Szanto AJ, Aldaz CM (2005) Frequent loss of WWOX expression in breast cancer: correlation with estrogen receptor status. Breast Cancer Res Treat 89:99–105

    Article  PubMed  PubMed Central  Google Scholar 

  26. Chang R, Song L, Xu Y, Wu Y, Dai C, Wang X, Sun X, Hou Y, Li W, Zhan X, Zhan L (2018) Loss of Wwox drives metastasis in triple-negative breast cancer by JAK2/STAT3 axis. Nat Commun 9(1):3486

    Article  PubMed  PubMed Central  Google Scholar 

  27. Ekizoglu S, Bulut P, Karaman E, Kilic E, Buyru N (2015) Epigenetic and genetic alterations affect the WWOX gene in head and neck squamous cell carcinoma. PLoS ONE. https://doi.org/10.1371/journal.pone.0115353

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank Helin Deniz Demir for the critical review of the article and the kind assistance in obtaining the patient’s samples. This study was supported by Tokat Gaziosmanpaşa University Scientific Research Projects Unit and TUBITAK. Project Nos. 2015/26 (Tokat Gaziosmanpaşa University) and 215S692 (TUBITAK).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nihan Bozkurt.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bozkurt, N., Ates, O. Analysis of WWOX gene expression and protein levels in pterygium. Int Ophthalmol 40, 1949–1953 (2020). https://doi.org/10.1007/s10792-020-01368-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10792-020-01368-7

Keywords

Navigation