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)

NDRG2 (N-myc downstream-regulated gene 2) is a candidate tumor suppressor implicated in control of glioblastoma proliferation and dendritic cell differentiation. The microphthalmia-associated transcription factor (Mitf) plays a crucial role in the melanocyte lineage and in melanoma by controlling survival, differentiation, cell cycle entry and exit, and melanoma metastasis. Identifying upstream regulators of Mitf expression, therefore, remains a key issue. In this study, we aimed to assess whether the candidate tumor suppressor NDRG2 can modulate Mitf expression. Here, we show that NDRG2 acts to prevent cAMP and beta-catenin-mediated activation of the Mitf promoter, thereby blocking melanogenesis via the downstream Mitf target genes Tyrosinase, Tyrp1 and Dct. The data suggest that NDRG2 impairs melanogenesis by interfering with both the TCF/beta-catenin and cAMP/CREB pathways that are known to stimulate Mitf expression in melanocytes and have major implications for the role of NDRG2 in pigmentation and melanoma progression. Taken together, the results not only identify NDRG2 as a novel regulator of pigmentation, but also potentially a key factor in regulating melanoma progression via Mitf.
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PMID:NDRG2 gene expression in B16F10 melanoma cells restrains melanogenesis via inhibition of Mitf expression. 1906 70

NDRG2, a member of the N-Myc downstream-regulated gene family, was shown to be a putative tumor suppressor gene in glioblastoma and other cancers. Through a bioinformatic analysis, we found that NDRG2 protein contains an acyl carrier domain. In the current study, we therefore hypothesized that NDRG2 may play an important role in the regulation of histone acetylation. Treatment of U251 and U87 glioma cells with trichostatin A, an inhibitor of histone deacetylase, upregulated the expression of NDRG2 and acetylated forms of histones H3 and H4, reduced tumor cell viability and arrested the cell cycle at the G1/G0 phase. Overexpression of NDRG2 by transfecting glioma cells with adenovirus containing the NDRG2 gene upregulated the levels of acetylated forms of H3 and H4 whereas inhibition of NDRG2 expression by siRNA-mediated knockdown downregulated the level of histone acetylation. Furthermore, NDRG2 siRNA significantly reduced the level of histone acetylation induced by trichostatin A. Taken together, these data demonstrate that NDRG2 can regulate the level of histone acetylation to control glioma cell growth.
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PMID:Regulation of histone acetylation by NDRG2 in glioma cells. 2191 36

Epigenetic alterations alone or in combination with genetic mechanisms play a key role in brain tumorigenesis. Glioblastoma is one of the most common, lethal and poor clinical outcome primary brain tumors with extraordinarily miscellaneous epigenetic alterations profile. The aim of this study was to investigate new potential prognostic epigenetic markers such as AREG, HOXA11, hMLH1, NDRG2, NTPX2 and Tes genes promoter methylation, frequency and value for patients outcome. We examined the promoter methylation status using methylation-specific polymerase chain reaction in 100 glioblastoma tissue samples. The value for clinical outcome was calculated using Kaplan-Meier estimation with log-rank test. DNA promoter methylation was frequent event appearing more than 45 % for gene. AREG and HOXA11 methylation status was significantly associated with patient age. HOXA11 showed the tendency to be associated with patient outcome in glioblastomas. AREG gene promoter methylation showed significant correlation with poor patient outcome. AREG methylation remained significantly associated with patient survival in a Cox multivariate model including MGMT promoter methylation status. This study of new epigenetic targets has shown considerably high level of analyzed genes promoter methylation variability in glioblastoma tissue. AREG gene might be valuable marker for glioblastoma patient survival prognosis, however further analysis is needed to clarify the independence and appropriateness of the marker.
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PMID:Promoter methylation of AREG, HOXA11, hMLH1, NDRG2, NPTX2 and Tes genes in glioblastoma. 2362 49

We analyzed the genome of a rhabdoid glioblastoma (R-GBM) tumor, a very rare variant of GBM. A surgical specimen of R-GBM from a 20-year-old woman was analyzed using whole exome sequencing (WES), whole transcriptome sequencing (WTS), single nucleotide polymorphism array, and array comparative genomic hybridization. The status of gene expression in R-GBM tissue was compared with that of normal brain tissue and conventional GBM tumor tissue. We identified 23 somatic non-synonymous small nucleotide variants with WES. We identified the BRAF V600E mutation and possible functional changes in the mutated genes, ISL1 and NDRG2. Copy number alteration analysis revealed gains of chromosomes 3, 7, and 9. We found loss of heterozygosity and focal homozygous deletion on 9q21, which includes CDKN2A and CDKN2B. In addition, WTS revealed that CDK6, MET, EZH2, EGFR, and NOTCH1, which are located on chromosomes 7 and 9, were over-expressed, whereas CDKN2A/2B were minimally expressed. Fusion gene analysis showed 14 candidate genes that may be functionally involved in R-GBM, including TWIST2, and UPK3BL. The BRAF V600E mutation, CDKN2A/2B deletion, and EGFR/MET copy number gain were observed. These simultaneous alterations are very rarely found in GBM. Moreover, the NDRG2 mutation was first identified in this study as it has never been reported in GBM. We observed a unique genomic signature in R-GBM compared to conventional GBM, which may provide insight regarding R-GBM as a distinct disease entity among the larger group of GBMs.
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PMID:Detection of a Distinctive Genomic Signature in Rhabdoid Glioblastoma, A Rare Disease Entity Identified by Whole Exome Sequencing and Whole Transcriptome Sequencing. 2631 Mar 74