Advertisement

Tumor Biology

, Volume 35, Issue 8, pp 7905–7909 | Cite as

Diversin is overexpressed in human gliomas and its depletion inhibits proliferation and invasion

  • Minghao Wang
  • Xinmiao Yu
  • Qianze Dong
  • Yunjie Wang
Research Article
  • 126 Downloads

Abstract

Previous study indicated diversin overexpression in human cancers. However, its expression pattern in human gliomas and the molecular mechanisms of diversin on cancer progression have not been characterized. In the present study, diversin expression was investigated in 105 glioma specimens using immunohistochemistry. Negative staining was observed in normal glial cells, and positive staining was found in 33 out of 105 (31.4 %) glioma specimens. Diversin overexpression correlated with advanced tumor grade (p < 0.05). Small interfering RNA (siRNA) knockdown was performed in U87 and TG905 cell lines with high endogenous diversin expression. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assay showed that diversin knockdown inhibited glioma cell growth. Matrigel invasion assay showed that diversin depletion inhibited cell invasion. In addition, messenger RNA (mRNA) and protein levels of matrix metallopeptidase 9 (MMP9) were downregulated after siRNA treatment. In conclusion, diversin is overexpressed in human glioma and regulates glioma cell proliferation and invasion, possibly through MMP9.

Keywords

Diversin Immunohistochemistry Glioma 

Notes

Conflicts of interest

None

References

  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics. CA Cancer J Clin. 2012;62(1):10–29.PubMedCrossRefGoogle Scholar
  2. 2.
    Krupkova Jr O, Loja T, Redova M, Neradil J, Zitterbart K, Sterba J, et al. Analysis of nuclear nestin localization in cell lines derived from neurogenic tumors. Tumour Biol. 2011;32(4):631–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Zadran S, Amighi A, Otiniano E, Wong K, Zadran H. ENTPD5-mediated modulation of ATP results in altered metabolism and decreased survival in gliomablastoma multiforme. Tumour Biol. 2012;33(6):2411–21.PubMedCrossRefGoogle Scholar
  4. 4.
    Feiguin F, Hannus M, Mlodzik M, Eaton S. The ankyrin repeat protein Diego mediates frizzled-dependent planar polarization. Dev Cell. 2001;1(1):93–101.PubMedCrossRefGoogle Scholar
  5. 5.
    Schwarz-Romond T, Asbrand C, Bakkers J, Kuhl M, Schaeffer HJ, Huelsken J, et al. The ankyrin repeat protein diversin recruits casein kinase iepsilon to the beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling. Genes Dev. 2002;16(16):2073–84.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Haribaskar R, Putz M, Schupp B, Skouloudaki K, Bietenbeck A, Walz G, et al. The planar cell polarity (PCP) protein diversin translocates to the nucleus to interact with the transcription factor AF9. Biochem Biophys Res Commun. 2009;387(1):212–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Moeller H, Jenny A, Schaeffer HJ, Schwarz-Romond T, Mlodzik M, Hammerschmidt M, et al. Diversin regulates heart formation and gastrulation movements in development. Proc Natl Acad Sci U S A. 2006;103(43):15900–5.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Ikeda M, Hirota Y, Sakaguchi M, Yamada O, Kida YS, Ogura T, et al. Expression and proliferation-promoting role of diversin in the neuronally committed precursor cells migrating in the adult mouse brain. Stem Cells. 2010;28(11):2017–26.PubMedCrossRefGoogle Scholar
  9. 9.
    Luan L, Zhao Y, Xu Z, Jiang G, Zhang X, Fan C, et al. Diversin increases the proliferation and invasion ability of non-small-cell lung cancer cells via JNK pathway. Cancer Lett. 2014;344(2):232–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Kim MS, Park MJ, Kim SJ, Lee CH, Yoo H, Shin SH, et al. Emodin suppresses hyaluronic acid-induced MMP-9 secretion and invasion of glioma cells. Int J Oncol. 2005;27(3):839–46.PubMedGoogle Scholar
  11. 11.
    Dong QZ, Wang Y, Tang ZP, Fu L, Li QC, Wang ED, et al. Derlin-1 is overexpressed in non-small cell lung cancer and promotes cancer cell invasion via EGFR-ERK-mediated up-regulation of MMP-2 and MMP-9. Am J Pathol. 2013;182(3):954–64.PubMedCrossRefGoogle Scholar
  12. 12.
    Sun C, Wang Q, Zhou H, Yu S, Simard AR, Kang C, et al. Antisense MMP-9 RNA inhibits malignant glioma cell growth in vitro and in vivo. Neurosci Bull. 2013;29(1):83–93.PubMedCrossRefGoogle Scholar
  13. 13.
    Takaesu G, Kang JS, Bae GU, Yi MJ, Lee CM, Reddy EP, et al. Activation of p38alpha/beta MAPK in myogenesis via binding of the scaffold protein JLP to the cell surface protein Cdo. J Cell Biol. 2006;175(3):383–8.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Garg M, Kanojia D, Khosla A, Dudha N, Sati S, Chaurasiya D, et al. Sperm-associated antigen 9 is associated with tumor growth, migration, and invasion in renal cell carcinoma. Cancer Res. 2008;68(20):8240–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Tang ZP, Cui QZ, Dong QZ, Xu K, Wang EH. Ataxia-telangiectasia group D complementing gene (ATDC) upregulates matrix metalloproteinase 9 (MMP-9) to promote lung cancer cell invasion by activating ERK and JNK pathways. Tumour Biol. 2013;34(5):2835–42.PubMedCrossRefGoogle Scholar
  16. 16.
    Wang Y, Dong Q, Miao Y, Fu L, Lin X, Wang E. Clinical significance and biological roles of SPAG9 overexpression in non-small cell lung cancer. Lung Cancer. 2013;81(2):266–72.PubMedCrossRefGoogle Scholar
  17. 17.
    Gutierrez GJ, Tsuji T, Cross JV, Davis RJ, Templeton DJ, Jiang W, et al. JNK-mediated phosphorylation of Cdc25C regulates cell cycle entry and G(2)/M DNA damage checkpoint. J Biol Chem. 2010;285(19):14217–28.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Minghao Wang
    • 1
  • Xinmiao Yu
    • 2
  • Qianze Dong
    • 3
  • Yunjie Wang
    • 1
  1. 1.Department of NeurosurgeryFirst Affiliated Hospital of China Medical UniversityShenyangPeople’s Republic of China
  2. 2.Department of Surgical Oncology and Breast SurgeryFirst Affiliated Hospital of China Medical UniversityShenyangChina
  3. 3.Department of PathologyFirst Affiliated Hospital of China Medical UniversityShenyangChina

Personalised recommendations