Publications (3)7.85 Total impact

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    ABSTRACT: Sterol regulatory element-binding protein-1a (SREBP1a) is a member of the SREBP family of transcription factors, which mainly controls homeostasis of lipids. SREBP1a can also activate the transcription of isocitrate dehydrogenase 1 (IDH1) by binding to its promoter region. IDH1 mutations, especially R132H mutation of IDH1, are a common feature of a major subset of human gliomas. There are few data available on the relationship between mutational IDH1 expression and SREBP1a pathway. In this study, we investigated cellular effects and SREBP1a pathway alterations caused by R132H mutational IDH1 expression in U87 cells. Two glioma cell lines, stably expressing mutational (U87/R132H) or wild type (U87/wt) IDH1, were established. A cell line, stably transfected with pcDNA3.1(+) (U87/vector), was generated as a control. Click-iT® EdU assay, sulforhodamine B assay, and wound healing assay respectively showed that the expression of R132H induced cellular proliferation, cell growth, and cell migration. Western blot revealed that SREBP1 was increased in U87/R132H compared with that in U87/wt. Elevated SREBP1a and several its target genes, but not SREBP1c, were detected by real-time polymerase chain reaction in U87/R132H. All these findings indicated that R132H mutational IDH1 is involved in the regulation of proliferation, growth, and migration of glioma cells. These effects may partially be mediated by SREBP1a pathway.
    Journal of Molecular Neuroscience 09/2012; 50(1). DOI:10.1007/s12031-012-9890-6 · 2.34 Impact Factor
  • Jian Zhu · Jianling Zuo · Qinian Xu · Xiuyun Wang · Zhong Wang · Dai Zhou
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    ABSTRACT: Gliomas are the most common human brain tumours and can be classified into four grades based on clinical and pathological criteria. A recent cancer genome-sequencing project revealed that more than 70% of low-grade gliomas bear mutations in one of two NAD(+)-dependent isocitrate dehydrogenase enzymes, namely, IDH1 and IDH2. Based on the findings that glioma-derived mutations in IDH1 can inhibit the catalytic activity of the enzyme, induce HIF-1α, and can produce 2-hydroxyglutarate, two research groups speculated that the IDH mutations may contribute to the promotion of tumorigenesis in gliomas. However, they cannot fully explain the phenomenon that patients harbouring such mutations usually have better outcomes than those with the wild-type IDH genes. This fact leads us to hypothesize that the IDH mutations are not the origin of gliomas but a subsequent protective mechanism that interferes with the metabolism of the tumour cells, making these cells fragile and susceptible to cell death. This process finally helps patients who harbour such IDH mutations to survive. Therefore, contrary to the proposals of other researchers, we speculate that any interventions that correct the impaired function of the mutant IDHs, such as the use of cell-permeable α-ketoglutarate derivatives, may not cure gliomas and may even worsen the disease.
    Medical Hypotheses 04/2011; 76(4):602-3. DOI:10.1016/j.mehy.2011.01.011 · 1.07 Impact Factor
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    Youxin Zhou · Fang Liu · Qinian Xu · Xiuyun Wang
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    ABSTRACT: Gliomas represent the most common primary malignant brain tumors, yet little is known about the molecular pathogenesis of these tumors. The highly-regulated Wnt signal transduction pathway is essential for normal developmental processes, and defects in the pathway are closely linked to oncogenesis. Dickkopf-1 (DKK-1) is a secreted protein that acts as a potent inhibitor of the Wnt pathway. The aim of this study was to examine the expression profile of DKK-1 gene in human glioma and its association with tumor malignancy. We determined the expression levels of DKK-1 transcript and protein in 12 glioblastoma cell lines, medulloblastoma cells, low-grade glioma cells, and human astrocyte cells by semiquantitative RT-PCR and ELISA. A total of 47 tumor biopsy specimens and 11 normal brain tissue samples from patients with cerebral trauma internal decompression were embedded in paraffin blocks and used for immunostaining. Twenty-six primary tumors and 7 corresponding brain samples were stored in liquid nitrogen and used for RT-PCR. We further examined serologic concentrations and cerebral fluid levels of DKK-1 in patients with tumors. DKK-1 could only be detected in 12 human glioblastoma cell lines, not in a panel of other tumor and normal cell lines. The difference between glioma patients and healthy individuals was significant. Kendall's tau-c association analysis also revealed the increased DKK-1 protein expression in tumor tissues of higher pathologic classification. The levels of cerebral fluid DKK-1 protein were significantly higher in glioma patients than in healthy donors or in neuronal benign tumor patients, suggesting that the DKK-1 molecule in cerebral fluids can be applicable to detect the presence of glioma and be developed as a novel prognostic treatment. The Wnt antagonist DKK-1 gene may have important roles in glioma tumorigenesis and act as a novel biomarker in human malignant glioblastoma.
    Journal of Experimental & Clinical Cancer Research 10/2010; 29(1):138. DOI:10.1186/1756-9966-29-138 · 4.43 Impact Factor