Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Integrated bioinformatic and wet-lab approach to identify potential oncogenic networks in neuroblastoma: MEIS1

ABSTRACT: The pediatric tumor neuroblastoma is the second cause of cancer-related death in children. Although several recurrent gene aberrations have been found, the main signaling networks in the neuroblastoma cell, that can give important clues for more specific, more efficient treatment, is still unknown. Here we demonstrate an analysis of the MEIS1 pathway in neuroblastic tumors. It suggests important regulatory connections to tumor differentiation, cell cycle, and cell death. Time-course experiment of MEIS1-shRNA induction, with 5 timepoints.

ORGANISM(S): Homo sapiens

SUBMITTER: Rogier Versteeg

PROVIDER: E-GEOD-17827 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Integrated bioinformatic and wet-lab approach to identify potential oncogenic networks in neuroblastoma: MSX1

Project description:mRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 (http://r2.amc.nl) in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGFM-NM-2 pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival. Triplicate time course experiments of MSX1 induction, with 4 timepoints.

2014-05-28 | E-GEOD-16481 | biostudies-arrayexpress

Analysis of TALE homeobox genes in neuroblastic tumors and Cell lines

Project description:This SuperSeries is composed of the following subset Series: GSE17827: Integrated bioinformatic and wet-lab approach to identify potential oncogenic networks in neuroblastoma: MEIS1 GSE18271: Analysis of TALE homeobox genes in neuroblastic tumors: ganglioneuroblastoma and ganglioneuroma Refer to individual Series

2012-09-24 | E-GEOD-18272 | biostudies-arrayexpress

Inactivation of CDK2 is synthetic lethal to MYCN-overexpressing cancer cells

Project description:Two genes have a synthetic lethal relationship when silencing or inhibition of one gene is only lethal in the context of a mutation or activation of the second gene. This situation offers an attractive therapeutic strategy, as inhibition of such a gene will only trigger cell death in tumor cells with an activated second oncogene but spare normal cells without activation of the second oncogene. Here we present evidence that CDK2 is synthetic lethal to neuroblastoma cells with MYCN amplification and overexpression. Neuroblastomas are childhood tumors with an often lethal outcome. Twenty percent of the tumors have MYCN amplification and these tumors are ultimately refractory to any therapy. Targeted silencing of CDK2 by three RNA interference techniques induced apoptosis in MYCN-amplified neuroblastoma cell lines, but not in MYCN single copy cells. Silencing of MYCN abrogated this apoptotic response in MYCN-amplified cells. Inversely, silencing of CDK2 in MYCN single copy cells did not trigger apoptosis, unless a MYCN transgene was activated. The MYCN induced apoptosis after CDK2 silencing was accompanied by nuclear stabilization of P53 and mRNA profiling showed up-regulation of P53 target genes. Silencing of P53 rescued the cells from MYCN-driven apoptosis. The synthetic lethality of CDK2 silencing in MYCN activated neuroblastoma cells can also be triggered by inhibition of CDK2 with a small molecule drug. Treatment of neuroblastoma cells with Roscovitine, a CDK inhibitor, at clinically achievable concentrations induced MYCN-dependent apoptosis. The synthetic lethal relation between CDK2 and MYCN indicates CDK2 inhibitors as potential MYCN-selective cancer therapeutics. CDK2 shRNA in a tet repressor system was stably transfected in the IMR32 cell line. Time course analysis was performed in triplicate after induction of CDK2 shRNA at 5 time points.

2014-05-19 | E-GEOD-16480 | biostudies-arrayexpress

NOTCH3 is a master-regulator of motility in neuroblastoma and is essential for cell survival

Project description:Migratory embryonal neuroblasts give rise to several tissues, including the sympathetic nervous system (SNS). Neuroblastomas are paediatric tumours of the peripheral SNS with a highly variable prognosis. We observed that high NOTCH3 expression in neuroblastomas correlated with a poor prognosis. Expression of a NOTCH3 transgene in neuroblastoma cells induced many motility genes and conferred a highly motile phenotype. Expression of these motility genes strongly correlated with NOTCH3 expression in neuroblastomas and many other tumours, suggesting a general role for NOTCH3 in regulation of these genes. Silencing of NOTCH3 or genes of the Notch-processing M-NM-3-secretase complex induced apoptosis in all neuroblastoma cell lines tested. These data suggest that NOTCH3 is a key-regulator of motility, and indispensable for survival of neuroblastoma cells. Time-course experiments of NOTCH3IC induction in two independent clones (c6 and c8), with 9 or 8 time points, respectively.

2013-08-06 | E-GEOD-16477 | biostudies-arrayexpress

Integrated bioinformatic and wet-lab approach to identify potential oncogenic networks in neuroblastoma: MYCN

Project description:mRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 (http://r2.amc.nl) in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGFÎ² pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival. Time-course experiments in triplicate of MYCN induction after doxycycline addition, with 7 timepoints.

2015-10-20 | E-GEOD-16478 | biostudies-arrayexpress

Analysis of TALE homeobox genes in neuroblastic tumors: ganglioneuroblastoma and ganglioneuroma

Project description:A large proportion of patients suffering from the malignant pediatric tumor neuroblastoma die of progressive disease despite intensive therapy. Neuroblastomas belong to the group of neuroblastic tumors, together with the more benign, differentiated ganglioneuroblastomas and ganglioneuromas. Little is known of the genes driving the differentiation processes in these tumor types. A search for the transcription factors differentially expressed between ganglioneuromas, ganglioneuroblastomas, and neuroblastomas in a series of 110 neuroblastic tumors (NB110) identified a large number of HOX- and TALE (Three Amino acid Loop Extension)-class homeobox transcription factor genes. The MEIS1-3, PBX1 and -3, and PKNOX1 TALE genes showed highest expression in neuroblastomas and lowest in ganglioneuromas and ganglioneuroblastomas. The PKNOX2 and TGIF1-2 genes showed the opposite expression pattern. This suggests an involvement of TALE genes in neuroblastoma differentiation. Expression of MEIS1, a known oncogene in haematopoietic tumors, was high in all neuroblastomas, and strongly correlated with undifferentiated histology. Consequently, we generated IMR-32 neuroblastoma cells capable of inducible shRNA-mediated MEIS1 knockdown. We observed differentiation, growth arrest and induction of apoptosis upon MEIS1 down-regulation. Affymetrix profiling of time-course experiments using these cells allowed the identification of MEIS1 target genes. Analysis of the target genes in the NB110 series showed that 323 of these were also significantly correlated to MEIS1 expression and to tumor differentiation in neuroblastic tumors. Genes involved in the cell cycle and in developmental pathways were over-represented in this gene set. We conclude that MEIS1 governs several of the signal transduction routes important for neuroblastoma survival and differentiation. 12 ganglioneuroma (gn) and 10 ganglioneuroblastoma (gnb) were analyzed.

2012-09-24 | E-GEOD-18271 | biostudies-arrayexpress

Integrated bioinformatic and wet-lab approach to identify potential oncogenic networks in neuroblastoma

Project description:mRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGFM-NM-2 pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival. 88 human Neuroblastoma samples were analyzed.

2012-03-08 | E-GEOD-16476 | biostudies-arrayexpress

EZH2 over-expression is associated with gain of chromosome arm 7q and essential for cell cycle progression and a marker of poor prognosis in neuroblastoma

Project description:Neuroblastoma is an often aggressive childhood cancer with several large chromosomal regions showing recurrent gains or losses. Chromosome 7q is gained in 40-60% of neuroblastomas, but despite being the second most frequent genomic aberration, no oncogenes have been linked to 7q gain. We performed expression profiling and array CGH on 88 primary neuroblastoma tumors to identify a 7q oncogene. We assayed neuroblastoma cell lines and combined bioinformatic analyses on the in vitro and in vivo data.

2013-10-06 | E-GEOD-28409 | biostudies-arrayexpress

IMR32 was transduced with control or shMYCN virus (duplo). For each experiment 3 time points were analyzed and 2 no virus controls.

Project description:IMR32 was transduced with control or shMYCN virus (duplo). For each experiment 3 time points were analyzed and 2 no virus controls. IMR32 was transduced with control or shMYCN virus (duplo). For each experiment 3 time points were analyzed and 2 no virus controls.

2012-11-05 | E-GEOD-39218 | biostudies-arrayexpress

Gene expression profiling in neuroblastoma cells upon CHAF1A silencing

Project description:We used an inducible ShRNA system and microarrays to detail the global programme of gene expression underlying neuroblastoma differentiation upon CHAF1A silencing . CHAF1A is a subunit of the Chromatin Assembly Factor-1 (CAF1) and regulates H3K9-trimethylation. High expression of CHAF1A strongly correlates with neuroblastoma poor prognosis and loss-of-function drives neuronal differentiation in vitro and in vivo. Total RNA was isolated using RNAeasy kit from IMR32 cells transduced with inducible CHAF1A ShRNA. Gene expression profiling was performed in neuroblastoma cells upon CHAF1A silencing over time course (0, 5, and 10 days) in triplicate.

2013-11-01 | E-GEOD-51978 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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