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
Beites CL, Xie H, Bowser R, Trimble WS (1999) The septin CDCrel-1 binds syntaxin and inhibits exocytosis. Nat Neurosci 2:434–439
Field CM, Kellogg D (1999) Septins: cytoskeletal polymers or signalling GTPases? Trends Cell Biol 9:387–394
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
Kartmann B, Roth D (2001) Novel roles for mammalian septins: from vesicle trafficking to oncogenesis. J Cell Sci 114:839–844
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
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
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
Hall PA, Jung K, Hillan KJ, Russell SE (2005) Expression profiling the human septin gene family. J Pathol 206:269–278
Jiang RC, Pu PY, Jiao BH (2002) The expression of CDC10 in gliomas. Chin J Clin Neurosci 10:227–229
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
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
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
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
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
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
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
Kinoshita M, Noda M (2001) Roles of septins in the mammalian cytokinesis machinery. Cell Struct Funct 26:667–670
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
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
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
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
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
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
Bähler J (2005) Cell-cycle control of gene expression in budding and fission yeast. Annu Rev Genet 39:69–94
Ohtsubo M, Roberts JM (1993) Cyclin-dependent regulation of G1 in mammalian fibroblasts. Science 259:1908–1912
Lee MH, Yang HY (2001) Negative regulators of cyclin-dependent kinases and their roles in cancers. Cell Mol Life Sci 58:1907–1922
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
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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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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