Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Systems-level analyses reveal a convergent pathway for progression of diffuse astrocytoma and potential role for resveratrol in delaying high-grade transformation

ABSTRACT: We assembled genome-wide gene regulatory networks (“modules”) that are differentially co-expressed between grade II and grade III IDH1-mutated astrocytomas in order to identify drivers of astrocytoma progression. We prioritized module M2 as a candidate module regulating glioma transformation on the basis that the module was enriched for cancer predisposition genes and had a pattern of expression in human glioma samples associated with both clinical progression and genomic aberrations in known cancer genes. M2 was functionally enriched for genes related to cell cycle regulation, and a genome-wide reverse engineering approach predicted the known cell cycle regulators FoxM1, B-Myb, and E2F2 as key transcriptional regulators of this module. Using separate drug-induced transcriptional perturbation data, we predicted that the naturally occurring polyphenol resveratrol down-regulates multiple nodes of M2. Transcriptional modulation of M2 by resveratrol and its predicted growth inhibitory effects was experimentally confirmed in vitro using low-passage primary human astrocytoma cells, including at nanomolar concentrations of resveratrol achievable in human cerebral spinal fluid from oral dosing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE117620 | GEO | 2019/10/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Affymetrix SNP array data for low-grade astrocytoma samples

Project description:Copy number analysis of 21 paediatric low-grade astrocytomas identified a discrete copy number gain of 1.9Mb in chromosome band 7q34. The gain was present in 12/14 cerebellar pilocytic astrocytomas. Subsequent analysis of tumour cDNA indentified a novel gene fusion between KIAA1549 and BRAF in these tumours. Copy number analysis of 21 paediatric low-grade astrocytomas using the Affymetrix GeneChip Human Mapping 250K Nsp Array. This study comprised 14 pilocytic astrocytomas, 4 diffuse astrocytomas, one pilomyxoid astrocytoma, one pilomyxoid glioma and one pleomorphic xanthoastrocytoma. Tumours were compared to the mean of two normal male DNA controls.

2010-04-09 | E-GEOD-14960 | biostudies-arrayexpress

Pilocytic astrocytoma

Project description:Pilocytic astrocytomas (PAs) are the most common glioma in children. While many PAs are slow growing or clinically indolent, others exhibit more aggressive features with tumor recurrence and death. In order to identify genetic signatures that might predict PA clinical behavior, we performed gene expression profiling on 41 primary PAs arising sporadically and in patients with neurofibromatosis type 1 (NF1). While no expression signature was found that could discriminate clinically-aggressive or recurrent tumors from more indolent cases, PAs arising in patients with NF1 did exhibit a unique gene expression pattern. In addition, we identified a gene expression signature that stratified PAs by location (supratentorial versus infratentorial). Keywords: Human, WHO grade I, Brain tumor, Pilocytic astrocytoma, NF1

2007-03-14 | GSE5675 | GEO

Mouse high grade astrocytoma cells (GL261) treated with neural stem/precursor cell (NPC) conditioned medium or non-conditioned medium (control)

Project description:Primary astrocytomas of high histopathological grade (HG-astrocytomas) are largely restricted to older patients and are almost invariably fatal despite multimodal therapy. Here, we show that the young brain has an endogenous defense mechanisms against HG-astrocytomas. Neural precursor cells (NPCs) migrate to HG-astrocytomas, reduce glioma expansion and prolong survival by releasing a group of fatty-acid ethanolamides that have agonistic activity on the vanilloid receptor (transient receptor potential vanilloid subfamily member-1; TRPV1). TRPV1 expression is much higher in HG-astrocytomas than in the tumor-free brain and TRPV1 stimulation triggers tumor cell-death via the activating transcription factor-3 (ATF3) controlled branch of the ER-stress pathway. The anti-tumourigenic response of NPCs is lost with aging. NPC-mediated tumor suppression can be mimicked in the old brain by systemic administration of the synthetic vanilloid Arvanil, indicating that TRPV1 agonists hold potential as new HG-astrocytoma therapeutics. The goal of this microarray study was understand how neural stem / precursor cell (NPC) induced high grade astrocytoma cell-death is controlled by changes in gene expression. We investigated the gene-expression pattern in mouse high grade astrocytoma GL261 cells after incubation with NPC non-conditioned medium (controls) or NPC-conditioned medium by microarrays and found that endoplasmic reticulum stress genes like the activating transcription factor-3 (ATF3) were robustly up-regulated in NPC-conditioned medium treated mouse high grade astrocytoma cells, compared to controls. Comparison of two experimental groups (conditioned medium treated versus non-conditioned medium treated) in three dye swap experiments (6 arrays used in total).

2012-04-30 | E-GEOD-37671 | biostudies-arrayexpress

The Transcriptomic Landscape of Pediatric Astrocytoma

Project description:Tumors of the central nervous system are the most common solid neoplasia during human childhood, representing one of the leading causes of cancer-related mortality. Tumors that originate from astrocyte cells (astrocytoma) in the brain are the most frequently found. According to their histological and pathological features, these tumors are classified into four categories. However, recently an extra layer of molecular classification of the tumorigenesis-associated genes IDH1/2 and H3F3A has been incorporated into the classification guidelines. While mutations in H3F3A are exclusively found in a subtype of pediatric astrocytoma grade IV, mutations in IDH1/2 are very rare in children younger than 14 years old. The transcriptomic profiles of astrocytoma in adults and children have been extensively studied however focusing on the study of the transcriptomic profile of the different grades of astrocytoma (including the additional layer of molecular classification) in pediatric populations are scarce. Therefore, we have profiled the transcriptomic landscape of the four grades of pediatric astrocytoma by RNA sequencing.

2022-10-25 | GSE196694 | GEO

Astrocytoma cell lines transduced to either express GFAP isoforms or to knockdown GFAP isoforms

Project description:Modulation of the GFAP cytoskeleton in astrocytoma cells alters processes involved in extracellular matrix remodelling and cell-cell signalling – a transcriptome analysis Astrocytomas grade IV are malignant brain tumours with no effective treatment and a five year survival rate of only 5%. Expression of Glial Fibrillary Acidic Protein (GFAP) is lower in high astrocytoma grade, but the expression of the splice isoform GFAPδ is similar in low and high-grade astrocytomas. Thus the ratio of GFAPδ/α is increased in high-grade astrocytomas. We studied transcriptome changes in astrocytoma cell lines resulting from an induced alteration of GFAP isoform expression. GFAPα or GFAPδ were increased or decreased by recombinant expression or shRNA mediated knockdown of GFAPpan or GFAPα. We find that the most prominent effects are induced by the modulations where the GFAPδ/GFAPα ratio is increased. Gene ontology analysis revealed that the main effects of GFAP modulation take place in the extracellular matrix remodelling and cellular signalling clusters, with possible implications in astrocytoma invasive behaviour and angiogenesis.

2017-07-03 | GSE74567 | GEO

Expression and differential expression analysis of astrocytoma patient samples (WHO grades I and III) and primary glioblastoma (WHO grade IV)

Project description:Expression and differential expression analysis of astrocytoma patient samples (WHO grades I and III) and primary glioblastoma (WHO grade IV). Expression and differential expression was assessed by using an Agilent custom microarray (244K). The custom array contains probes for genomic regions that have been found to be differentially expressed (i) throughout cell cycle progression, (ii) in response to the anti-proliferative and pro-apoptotic p53 pathway, and (iii) the anti-apoptotic and pro-proliferative STAT-3 pathway by employing TAS (Kampa et al. "Novel RNAs identified from an in-depth analysis of the transcriptome of human chromosomes 21 and 22". Genome Research, 14:331-42, 2004). In addition, the Agilent custom array (244K) interrogates probes for genomic regions predicted to contain a conserved secondary structure identified by RNAz (Washietl et al. "Fast and reliable prediction of noncoding RNAs." Proc Natl Acad Sci USA. 102:2454-9, 2005.) or Evofold (Pedersen et al. "Identification and classification of conserved RNA secondary structures in the human genome." PLoS Comput Biol. 2:e33, 2006.), as well as known non-coding RNAs from public databases, and the Agilent mRNA probe set 014850. We analyzed four arrays each for astrocytoma patient samples of grade I, grade III and grade IV.

2014-02-04 | E-GEOD-43911 | biostudies-arrayexpress

Human Pilocytic Astrocytoma Single Cell RNA Sequencing

Project description:<p>Pilocytic astrocytoma (PA), the most common childhood brain tumor, is a low-grade glioma with a single driver BRAF rearrangement. Here, we perform scRNAseq in six PAs using methods that enabled detection of the rearrangement. When compared to higher-grade gliomas, a strikingly higher proportion of the PA cancer cells exhibit a differentiated, astrocyte-like phenotype. A smaller proportion of cells exhibit a progenitor-like phenotype with evidence of proliferation. These express a mitogen-activated protein kinase (MAPK) program that was absent from higher-grade gliomas. Immune cells, especially microglia, comprise 40% of all cells in the PAs and account for differences in bulk expression profiles between tumor locations and subtypes. These data indicate that MAPK signaling is restricted to relatively undifferentiated cancer cells in PA, with implications for investigational therapies directed at this pathway.</p> <p>Note that 931 out of 1234 samples in the Sequence Read Archive (SRA) passed QC and have transcript count data available from the Broad Institute Single Cell Portal. The transcript count data can be found at <a href="https://singlecell.broadinstitute.org/single_cell/study/SCP271/pilocytic-astrocytoma-single-cell-rna-seq#study-download" target="_blank">https://singlecell.broadinstitute.org/single_cell/study/SCP271/pilocytic-astrocytoma-single-cell-rna-seq#study-download</a></p>

| phs001854 | dbGaP

Differentially Expressed LncRNAs Might be Controlling Signaling Pathways by Establishing Interactions with mRNAs and MicroRNAs in Pediatric Astrocytoma

Project description:In this study was determined the global expression pattern of long non-coding RNAs, mRNAs, and miRNAs in pediatric astrocytoma of different histological grades. The Affymetrix HTA 2.0 array showed expression changes on one hundred-sixty two and two hundred-fifteen long non-coding RNAs in tumors (versus the control) and in GBM (versus low-grade astrocytoma), respectively. A total of seven astrocytic tumors and two control tissues were collected during the period of 2012–2014: four low-grade Ast (three pilocytic Ast (PAst) and one diffuse Ast (DAst)) and four high-grade Ast (four glioblastoma multiforme (GBM)).RNA was extracted from tissue samples using TRIzol (Ambion life technologies, Thermo Scientific Inc.) following the methodology described by Hongbao et al. 2008 and with certain modifications described by Vujovic et al. 2013. For expression analysis, Human Transcriptome Array 2.0 (HTA) (Santa Clara, CA, USA) was employed. in this study was determined the global expression pattern of long non-coding RNAs, mRNAs, and miRNAs in pediatric astrocytoma of different histological grades. The HTA 2.0 array showed expression changes on one hundred-sixty two and two hundred-fifteen long non-coding RNAs in tumors (versus the control) and in GBM (versus low-grade astrocytoma), respectively.

2015-08-25 | E-GEOD-72269 | biostudies-arrayexpress

Differentially Expressed LncRNAs Might be Controlling Signaling Pathways by Establishing Interactions with mRNAs and MicroRNAs in Pediatric Astrocytoma

2015-08-25 | GSE72269 | GEO

ECT2 and AURKB Modulate Formation of Stress Granules Containing Transcripts from Diverse Cellular Pathways in Astrocytoma Cells

Project description:Stress granules are small RNA-protein granules that modify the translational landscape during cellular stress to promote survival. The RhoGTPase RhoA is implicated in the formation of RNA stress granules. Our data demonstrate that the cytokinetic proteins ECT2 and AurkB are localized to stress granules in human astrocytoma cells. AurkB and its downstream target histone-3 are phosphorylated during arsenite-induced stress. Chemical (AZD1152-HQPA) and siRNA inhibition of AurkB results in fewer and smaller stress granules when analyzed utilizing high throughput fluorescent based cellomics assays. RNA immunoprecipitation with the known stress granule aggregates TIAR and G3BP1 was performed on astrocytoma cells and subsequent analysis revealed that astrocytoma stress granules harbour unique mRNAs for various cellular pathways including cellular migration, metabolism, translation and transcriptional regulation. Human astrocytoma cell stress granules contain mRNA that are known to be involved in glioma signaling and the mTOR pathway. These data provide evidence that RNA stress granules are a novel form of epigenetic regulation in astrocytoma cells, which may be targetable by chemical inhibitors and enhance astrocytoma susceptiblity to conventional therapy such as radiation and chemotherapy.

2016-02-29 | GSE76814 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data