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Overexpression of septin 7 suppresses glioma cell growth

  • Laboratory Investigation - Human/Animal Tissue
  • Published:
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Abstract

Our previous study demonstrated that SEPT7 was downregulated at mRNA level in human gliomas. This study is to further examine the expression of SEPT7 in glioma samples and characterizes its role on cell cycle progression and growth of glioma cells. mRNA and protein expression of SEPT7 were detected by RT-PCR, immunohistochemical staining, and western blot analysis in human glioma specimens and normal brain tissues. A pcDNA3-SEPT7 expression plasmid was constructed and transfected into human glioblastoma cell line U251, and cell proliferation and apoptosis were examined. The growth of established U251 and TJ905 subcutaneous xenograft gliomas was measured in nude mice treated with pcDNA3-SEPT7 and U251 xenograft tumors treated with SEPT7 siRNA. SEPT7 expression is negatively correlated with the increase of glioma grade. Overexpression of SEPT7 is able to inhibit cell proliferation and arrest cell cycle progression in the G0/G1 phase both in vitro and in vivo. Knocking down further the already low endogenous expression of SEPT7 in U251 xenograft tumors with siRNA leads to faster tumor growth compared with control tumors. This study demonstrates that SEPT7 is involved in gliomagenesis and suppresses glioma cell growth.

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References

  1. Beites CL, Xie H, Bowser R, Trimble WS (1999) The septin CDCrel-1 binds syntaxin and inhibits exocytosis. Nat Neurosci 2:434–439

    Article  CAS  PubMed  Google Scholar 

  2. Field CM, Kellogg D (1999) Septins: cytoskeletal polymers or signalling GTPases? Trends Cell Biol 9:387–394

    Article  CAS  PubMed  Google Scholar 

  3. Larisch S, Yi Y, Lotan R, Kerner H, Eimerl S, Tony Parks W, Gottfried Y, Birkey Reffey S, de Caestecker MP, Danielpour D, Book-Melamed N, Timberg R, Duckett CS et al (2000) A novel mitochondrial septin-like protein, ARTS, mediates apoptosis dependent on its P-loop motif. Nat Cell Biol 2:915–921

    Article  CAS  PubMed  Google Scholar 

  4. Kartmann B, Roth D (2001) Novel roles for mammalian septins: from vesicle trafficking to oncogenesis. J Cell Sci 114:839–844

    CAS  PubMed  Google Scholar 

  5. Nakatsuru S, Sudo K, Nakamura Y (1994) Molecular cloning of a novel human cDNA homologous to CDC10, in Sacharomyces cerevisiae. Biochem Biophys Res Commun 202:82–87

    Article  CAS  PubMed  Google Scholar 

  6. Whitehall S, Stacey P, Dawson K, Jones (1999) Cell cycle-regulated transcription in fission yeast: Cdc10-Res protein interactions during the cell cycle and domains required for regulated transcription. Mol Biol Cell 10:3705–3715

    CAS  PubMed  Google Scholar 

  7. Uzawa S, Li F, Jin Y, McDonald KL, Braunfeld MB, Agard DA, Cande WZ (2004) Spindle pole body duplication in fission yeast occurs at the G1/S boundary but maturation is blocked until exit from S by an event downstream of cdc10+. Mol Biol Cell 15:5219–5230

    Article  CAS  PubMed  Google Scholar 

  8. Hall PA, Jung K, Hillan KJ, Russell SE (2005) Expression profiling the human septin gene family. J Pathol 206:269–278

    Article  CAS  PubMed  Google Scholar 

  9. Jiang RC, Pu PY, Jiao BH (2002) The expression of CDC10 in gliomas. Chin J Clin Neurosci 10:227–229

    Google Scholar 

  10. Jiang RC, Pu PY, Shen CH (2004) Preliminary study on cancer-related gene expression profiles in 63 cases of gliomas by cDNA array. Chin J Neurosurg 20:18–21

    Google Scholar 

  11. Jia ZF, Pu PY, Kang CS et al (2007) Influence of SEPT7 on biological characters of glioma cell line TJ905. Zhonghua Wai Ke Za Zhi 45(20):1420–1423

    PubMed  Google Scholar 

  12. Xu S, Jia ZF, Huang Q et al (2008) Study on the anti-invasion effect of SEPT7 gene for U251MG glioma cell in vitro. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 25(3):262–267

    CAS  PubMed  Google Scholar 

  13. Wang SL, Li F, Pu PY (1996) Establishment and characterization of two human glioblastoma cell lines: TJ899 and TJ905 (in Chinese). Tianjin Med J 24:416–418

    Google Scholar 

  14. Pu PY, Zhong Y, Wang SL (1992) Construction and comparison on the characters of primary and recurrent malignant astrocytoma cell TJ899 and TJ905 cell lines (in chinese). Chin J Neurosurg 8:38–40

    Google Scholar 

  15. Kang CS, Pu PY, Li J, Wang GX (2004) Inhibitory effect of antisense and dominant-negative AKT2 constructs on proliferation of glioma cell line TJ905. Ai Zheng 23:1267–1272

    CAS  PubMed  Google Scholar 

  16. Kang CS, Zhang ZY, Jia ZF, Wang GX, Qiu MZ, Zhou HX, Yu SZ, Chang J, Jiang H, Pu PY (2006) Suppression of EGFR expression by antisense or small interference RNA inhibits U251 glioma cell growth in vitro and in vivo. Cancer Gene Ther 13:530–538

    Article  CAS  PubMed  Google Scholar 

  17. Kinoshita M, Noda M (2001) Roles of septins in the mammalian cytokinesis machinery. Cell Struct Funct 26:667–670

    Article  CAS  PubMed  Google Scholar 

  18. Scott M, Hyland P, McGregor G, Hillan KJ, Russell SE, Hall PA (2005) Multimodality expression profiling shows SEPT9 to be overexpressed in a wide range of human tumours. Oncogene 24:4688–4700

    Article  CAS  PubMed  Google Scholar 

  19. Amir S, Wang R, Matzkin H, Simons JW, Mabjeesh NJ (2006) MSF-A interacts with hypoxia-inducible factor-1alpha and augments hypoxia-inducible factor transcriptional activation to affect tumorigenicity and angiogenesis. Cancer Res 66:856–866

    Article  CAS  PubMed  Google Scholar 

  20. Gottfried Y, Rotem A, Lotan R, Steller H, Larisch S (2004) The mitochondrial ARTS protein promotes apoptosis through targeting XIAP. EMBO J 23:1627–1635

    Article  CAS  PubMed  Google Scholar 

  21. Elhasid R, Sahar D, Merling A, Zivony Y, Rotem A, Ben-Arush M, Izraeli S, Bercovich D, Larisch S (2004) Mitochondrial pro-apoptotic ARTS protein is lost in the majority of acute lymphoblastic leukemia patients. Oncogene 23:5468–5475

    Article  CAS  PubMed  Google Scholar 

  22. Sakai K, Kurimoto M, Tsugu A, Hubbard SL, Trimble WS, Rutka JT (2002) Expression of Nedd5, a mammalian septin, in human brain tumors. J Neurooncol 57:169–177

    Article  PubMed  Google Scholar 

  23. Nagata T, Takahashi Y, Asai S, Ishii Y, Mugishima H, Suzuki T, Chin M, Harada K, Koshinaga S, Ishikawa K (2000) The high level of hCDC10 gene expression in neuroblastoma may be associated with favorable characteristics of the tumor. J Surg Res 92:267–275

    Article  CAS  PubMed  Google Scholar 

  24. Bähler J (2005) Cell-cycle control of gene expression in budding and fission yeast. Annu Rev Genet 39:69–94

    Article  PubMed  Google Scholar 

  25. Ohtsubo M, Roberts JM (1993) Cyclin-dependent regulation of G1 in mammalian fibroblasts. Science 259:1908–1912

    Article  CAS  PubMed  Google Scholar 

  26. Lee MH, Yang HY (2001) Negative regulators of cyclin-dependent kinases and their roles in cancers. Cell Mol Life Sci 58:1907–1922

    Article  CAS  PubMed  Google Scholar 

  27. Kremer BE, Adang LA, Macara IG (2007) Septins regulate actin organization and cell cycle arrest through SOCS7-mediated nuclear accumulation of NCK. Cell 130(5):837–850

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by National Natural Science Foundation of China (Grant No: 30500523, Grant No: 30872985), the Program for New Century Excellent Talents in University (Grant No: NCET-07-0615), the Tianjin Education Commission (Grant No: 20070234), and the Tianjin Municipal Science and Technology Commission (Grant No: 06YFSZSF01100).

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Correspondence to Pei-yu Pu.

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Zhi-fan Jia and Qiang Huang contribute equally to this work.

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Jia, Zf., Huang, Q., Kang, Cs. et al. Overexpression of septin 7 suppresses glioma cell growth. J Neurooncol 98, 329–340 (2010). https://doi.org/10.1007/s11060-009-0092-1

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  • DOI: https://doi.org/10.1007/s11060-009-0092-1

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