Overexpression of septin 7 suppresses glioma cell growth

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.

The expression and functional characterization associated with cell apoptosis and proteomic analysis of the novel gene MLAA-34 in U937 cells

“…As the trigger of TBK-1 pathway, TBK1 is important for tumor angiogenesis and tumor-associated microvascular inflammation and expressed at significant levels in many solid tumors (19,20). A recent study has demonstrated that SEPT7 could function in gliomagenesis and in the suppression of glioma cell proliferation (21).…”

Septin roles in tumorigenesis

“…Overexpression of SEPT7 inhibits cell proliferation and arrests cell cycle progression in the G0/G1 phase both in vitro and in vivo. Complete depletion of Sept7 in glioma xenografts results in faster tumor growth compared with control tumors (Jia et al, 2010). SEPT2 is downregulated in gliomas (Khalil, 2007), whereas SEPT3 was reported to be upregulated in teratocarcinoma cells induced to undergo neuronal differentiation (Methner et al, 2001).…”

“…Gene fusion AML (Ono et al, 2002;Kadkol et al, 2006;Cerveira et al, 2008) Melanoma (Jaeger et al, 2007) SEPT7 Downregulation Glioma (Nagata et al, 2000;Jiang, 2002;Jiang, 2004;Jia et al, 2010;Tanaka et al, 2010) SEPT8 None None None SEPT9 Amplification/ Breast (Montagna et al, 2003;Scott et al, 2005;overexpression Gonzalez et al, 2007overexpression Gonzalez et al, , 2009) Upregulation Ovary Gene fusion AML, ALL (Strehl et al, 2006;Gulten et al, 2009;Saito et al, 2010) (Santos et al, 2010a,b) (Osaka et al, 1999;Yamamoto et al, 2002;Strehl et al, 2006;Kreuziger et al, 2007) Hypermethylation Colon and head and neck (He et al, 2010;Tierling et al, 2010;Quyun et al, 2010) (Grutzmann et al, 2008;deVos et al, 2009) (Bennett et al, 2008;Lofton-Day et al, 2008;Stanbery et al, 2010) Deletion Ovary, breast Russell et al, 2000) Hodgkin lymphoma (Giefing et al, 2008) SEPT10 None None SEPT11 Gene fusion Deletion AML (Santos et al, 2010b;Stevens et al, 2010) Deletion Liver SEPT12 None None SEPT13 None None SEPT14 None None (Montagna et al, 2003) and the Russell group established that SEPT9 overexpression occurs in various human tumors (Scott et al, 2005). The discovery of DNA hypermethylation at the promoter region of SEPT9 in colorectal (deVos et al, 2009) and head and neck cancer patients (Bennett et al, 2008) complicated the conflicti...…”

High methylation of the SEPT9 gene in Chinese colorectal cancer patients

“…The association of septins with actin and tubulin are required in cytokinesis (Spiliotis et al, 2005;Kinoshita, 2006). Due to their essential role in cell division and polarity, it is not surprising that septins were also reported to be key players in tumorigenesis (Osaka et al, 1999;Garcia-Fernandez et al, 2010;Jia et al, 2010). SEPT9 has been found to act as an oncogene and tumor suppressor gene in different types of cancers.…”