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.

Overexpression of septin 7 suppresses glioma cell growth

Correction: MiR-30a-5p Antisense Oligonucleotide Suppresses Glioma Cell Growth by Targeting SEPT7

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by targeting the mRNAs of hundreds of human genes. Variations in miRNA expression levels were shown to be associated with glioma. We have previously found miR-30a-5p overexpression in glioma cell lines and specimens. Bioinformatics analyses predict that several miRNAs, including miR-30a-5p, are involved in the post-transcriptional regulation of SEPT7. SEPT7 is a member of the septin family, which is a highly conserved subfamily of GTPases implicated in exocytosis, apoptosis, synaptogenesis, neurodegeneration and tumorigenesis. Our previous study has also demonstrated that SEPT7 expression is decreased in astrocytic gliomas with different grades and plays a tumor suppressor role. In the present study, we knocked down miR-30a-5p with antisense oligonucleotide (miR-30a-5p AS) in LN229 and SNB19 glioblastoma(GBM) cells, and found that cell growth and invasion were inhibited, while apoptosis was induced. miR-30a-5p AS treated cells showed upregulation of SEPT7 and downregulation of PCNA, cyclin D1, Bcl2, MMP2 and MMP9. In contrast, when miR-30a-5p mimics were transfected into LN229 and SNB19 GBM cells, cell growth and invasion were promoted and the expression of relevant proteins increased. Meanwhile, the effect of miR-30a-5p mimics on glioma cells can be reversed by transfection of SEPT7 construct. Additionaly, miR-30a-5p directly targeting SEPT7 was identified by the reporter gene assay. Our study demonstrates,for the first time, that miR-30a-5p is a bona fide negative regulator of SEPT7 and the oncogenic activity of miR-30a-5p in human gliomas is at least in part through the repression of SEPT7.

/pdf/mir-30a-5p-antisense-oligonucleotide-suppresses-glioma-cell-4toatnv6by.pdf

MiR-30a-5p Antisense Oligonucleotide Suppresses Glioma Cell Growth by Targeting SEPT7

Septins are a family of cytoskeleton related proteins consisting of 14 members that associate and interact with actin and tubulin From yeast to humans, septins maintain a conserved role in cytokinesis and they are also involved in a variety of other cellular functions including chromosome segregation, DNA repair, migration and apoptosis Tumorigenesis entails major alterations in these processes A substantial body of literature reveals that septins are overexpressed, downregulated or generate chimeric proteins with MLL in a plethora of solid tumors and in hematological malignancies Thus, members of this gene family are emerging as key players in tumorigenesis The analysis of septins during cancer initiation and progression is challenged by the presence of many family members and by their potential to produce numerous isoforms However, the development and application of advanced technologies is allowing for a more detailed analysis of septins during tumorigenesis Specifically, such applications have led to the establishment and validation of SEPT9 as a biomarker for the early detection of colorectal cancer This review summarizes the current knowledge on the role of septins in tumorigenesis, emphasizing their significance and supporting their use as potential biomarkers in various cancer types

Septin roles in tumorigenesis.

miR-19a/b promote EMT and proliferation in glioma cells via SEPT7-AKT-NF-κB pathway

Aim:To explore the expression of CDC10 in human astrocytic gliomas with cDNA array Methods:17 research samples of different types of astrocytic gliomas were acquired during operation After isolation of the total RNAs, the 32 P labeled cDNA probes were generated by reverse transcription and then hybridized to the Atlas cDNA array The gene expression profiles of tumors were obtained, which were then compared to one of the normal brain tissue individually The result was confirmed with Semi quantitative RT PCRResults:CDC10 were under expressed in all tumors when compared with the normal brain tissue It was revealed by RT PCR that the mRNA was dim or not detectable in tumors comparing to the high level in the normal brain tissue Conclusion:It is helpful to reveal the new function of the known gene to profile gene expressions parallelly by the cDNA array CDC10 are under expressed in astrocytic gliomas with their real function to be further analyzed

Expression of CDC10 in Gliomas

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Expression of CDC10 in Gliomas