Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With its growth characteristic and chemoresistance, glioblastoma is the most deadly brain tumor. Twenty-five core genes that influence the chemosensitivity of glioblastoma were screened in our previous experiments, and Id2, the inhibitor of DNA binding 2, an oncogene encoding a helix-loop-helix protein, was identified. The elevated expression levels of Id2 have been reported in several malignancies. The aim of this study is to investigate the effects of Id2 expression on the chemosensitivity of glioma cells. In this study, Id2 expression was investigated in a malignant glioma cell line. Then, we silenced the expression of Id2 with the highly specific posttranscriptional suppression of RNA interference (RNAi) in U87 cells. The changes in response to antitumor agents Me-CCNU, VM26, and TMZ were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was measured using an annexin V-fluorescein isothiocyanate (FITC) apoptosis detection kit. The relationship between Id2 expression and caspase 3 was tested by RT-PCR and Western blot. This study demonstrated that Id2 was significantly upregulated in glioma tissues, and Id2 correlated well with the advancement of glioma grade and a worse prognosis in response to temozolomide treatment. The RNAi-mediated decrease of Id2 expression enhanced chemosensitivity to Me-CCNU, VM26, and TMZ in the U87 cell line. We further discovered that silencing of Id2 expression could promote apoptosis of glioblastoma cells, which could be attributed to the fact that Id2 affects tumor cell chemosensitivity. Downregulation of the Id2 gene by RNAi could increase the chemosensitivity of glioblastoma cells. Id2 could be a good molecular target for glioblastoma gene therapy.
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PMID:Downregulation of Id2 increases chemosensitivity of glioma. 2577 86

Tumor cells proliferate in cellular environments characterized by a lack of optimal tissue organization resulting oftentimes in compromised cellular metabolism affecting nutrition, respiration, and energetics. The response of tumor cells to adverse environmental conditions is a key feature affecting their pathogenicity. We found that inhibitor of DNA binding 2 (ID2) expression levels significantly correlate with the ability of glioblastoma (GBM)-derived cell lines to survive glucose deprivation. ID2 suppressed mitochondrial oxidative respiration and mitochondrial ATP production by regulating the function of mitochondrial electron transport chain (mETC) complexes, resulting in reduced superoxide and reactive oxygen species (ROS) production from mitochondria. ID2 suppression of ROS production reduced mitochondrial damage and enhanced tumor cell survival during glucose deprivation. Bioinformatics analysis of GBM gene expression data from The Cancer Genome Atlas (TCGA) database revealed that expression of ID2 mRNA is unique among ID gene family members in correlating with the expression of nuclear genes involved in mitochondrial energy metabolism and assembly of mETC. Our data indicate that the expression level of ID2 in GBM cells can predict the sensitivity of GBM-derived tumor cells to decreased glucose levels. Low levels of ID2 expression in human GBM tissues may identify a clinical group in which metabolic targeting of glycolytic pathways can be expected to have the greatest therapeutic efficacy.
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PMID:ID2 promotes survival of glioblastoma cells during metabolic stress by regulating mitochondrial function. 2820 87