Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression analysis of superior cervical ganglion from backcrossed TH-MYCN transgenic mice

ABSTRACT: Neuroblastoma susceptibility in TH-MYN mice is heavily influence by mouse strain background. We have combined linkage analysis of tumor susceptibility with expression QTL analysis of superior cervical ganglia (pure peripheral symptathetic nervous tissue) to identify genes underlying tumor formation The development of targeted therapeutics for neuroblastoma, the third most common tumor in children, has been limited by a poor understanding of growth signaling mechanisms unique to the peripheral nerve precursors from which tumors arise. In this study, we combined genetics with gene expression analysis in the peripheral sympathetic nervous system to implicate arginase 1 and GABA signaling in tumor formation in vivo. In human neuroblastoma cells, activation of GABA-A receptors by a benzodiazepine induced apoptosis and inhibited mitogenic signaling through AKT and MAPK. These results suggest that GABA influences both neural development and neuroblastoma, and that benzodiazepines in clinical use may have potential for neuroblastoma therapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE59675 | GEO | 2015/01/30

SECONDARY ACCESSION(S): PRJNA255915

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression analysis of superior cervical ganglion from backcrossed TH-MYCN transgenic mice

Project description:Neuroblastoma susceptibility in TH-MYN mice is heavily influence by mouse strain background. We have combined linkage analysis of tumor susceptibility with expression QTL analysis of superior cervical ganglia (pure peripheral symptathetic nervous tissue) to identify genes underlying tumor formation The development of targeted therapeutics for neuroblastoma, the third most common tumor in children, has been limited by a poor understanding of growth signaling mechanisms unique to the peripheral nerve precursors from which tumors arise. In this study, we combined genetics with gene expression analysis in the peripheral sympathetic nervous system to implicate arginase 1 and GABA signaling in tumor formation in vivo. In human neuroblastoma cells, activation of GABA-A receptors by a benzodiazepine induced apoptosis and inhibited mitogenic signaling through AKT and MAPK. These results suggest that GABA influences both neural development and neuroblastoma, and that benzodiazepines in clinical use may have potential for neuroblastoma therapy. 224 backcrossed mice were genotyped at 349 markers to identify susceptibility loci for neuroblastoma. Gene expression from Superior Cervical Ganglia from 116 of these mice were correlated with genotyping data to identify putative eQTL.

2015-01-30 | E-GEOD-59675 | biostudies-arrayexpress

Inhibitory and Excitatory Synaptic Neuroadaptations in the diazepam tolerant brain

Project description:Benzodiazepine (BZ) drugs treat seizures, anxiety, insomnia, and alcohol withdrawal by potentiating γ2 subunit containing GABA type A receptors (GABAARs). BZ clinical use is hampered by tolerance and withdrawal symptoms, which include heightened seizure susceptibility, panic, and sleep disturbances. Here, we undergo a comprehensive investigation of inhibitory GABAergic and excitatory glutamatergic plasticity in mice tolerant to benzodiazepine sedation. Using quantitative proteomics approaches, we reveal cortex neuroadaptations of key pro-excitatory mediators and synaptic plasticity pathways, highlighted by Ca2+/calmodulin-dependent protein kinase II (CAMKII), MAPK, and PKC signaling.

2023-10-24 | PXD041332 | Pride

c-MYC drives neuroblastoma tumorigenesis and retinoic acid resistance in zebrafish [RNA-Seq]

Project description:Neuroblastoma is an often intractable tumor that accounts for 15% of childhood cancer deaths. In addition to MYCN amplification in 20% of tumors, 11% express high levels of c-MYC (MYC) protein. To study this newly defined subgroup, we have created a novel transgenic zebrafish model in which overexpression of MYC in the peripheral sympathetic nervous system drives early-onset neuroblastoma.

2019-06-01 | GSE99567 | GEO

c-MYC drives neuroblastoma tumorigenesis and retinoic acid resistance in zebrafish [ATAC-Seq]

2019-06-01 | GSE99566 | GEO

ASCL1 is directly activated by the LMO1 and MYCN oncogenes and is a master regulator of the differentiation program in neuroblastoma

Project description:Neuroblastoma is an embryonal tumor of the peripheral sympathetic nervous system. Elevated expression of the transcription factor LMO1 and the polymorphisms within this gene are associated with the susceptibility to develop neuroblastoma. LMO1 has been implicated as an oncogene in T-cell acute lymphoblastic leukemia; however, the transcriptional targets regulated by this protein in neuroblastoma cells are unknown. Here, we identify the genes and molecular pathways controlled by LMO1 in neuroblastoma cells. ChIP-seq analysis revealed that LMO1-bound regions are frequently co-occupied by GATA3 and MYCN proteins and are associated with active histone marks in neuroblastoma cells. RNA-seq analysis demonstrated that LMO1 regulates gene expression in a tumor type-specific manner. One high-confidence target gene directly regulated by LMO1 and MYCN is ASCL1, which is more highly expressed in adrenergic subtype of neuroblastoma cells as compared to normal neuronal cells. High levels of ASCL1 expression are associated with inferior overall survival in primary human neuroblastoma cases. ChIP-seq analysis identified a regulatory element controlling ASCL1 expression that is bound by LMO1, MYCN and the members of the core regulatory circuitry in neuroblastoma cells. Furthermore, ASCL1 is required for neuroblastoma cell growth and regulates genes responsible for repression of neuronal cell differentiation. Taken together, our results implicate ASCL1 as a critical downstream target of LMO1 in the molecular pathogenesis of neuroblastoma.

2019-11-09 | GSE120074 | GEO

FOXO3a Is A Major Target Of Inactivation By PI3K/AKT Signaling In Aggressive Neuroblastoma

Project description:Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with a highly variable prognosis. Activation of the PI3K/AKT pathway in neuroblastoma is correlated with poor patient prognosis, but the precise downstream effectors mediating this effect have not been determined. Here, we identify the forkhead transcription factor FOXO3a as a key target of the PI3K/AKT pathway in neuroblastoma. FOXO3a expression was elevated in low stage neuroblastoma tumors and normal embryonal neuroblasts, but reduced in late stage neuroblastoma. Inactivation of FOXO3a by AKT was essential for neuroblastoma cell survival. Treatment of neuroblastoma cells with the dual PI3K/mTOR inhibitor PI-103 activated FOXO3a and triggered apoptosis. This effect was rescued by FOXO3a silencing. Conversely, apoptosis induced by PI-103 or the AKT inhibitor MK-2206 was potentiated by FOXO3a overexpression. Further, levels of total or phosphorylated FOXO3a correlated closely with apoptotic sensitivity to MK-2206. In clinical specimens, there was an inverse relationship between gene expression signatures regulated by PI3K signaling and FOXO3a transcriptional activity. Moreover, high PI3K activity and low FOXO3a activity were each associated with an extremely poor prognosis. Our work indicates that expression of FOXO3a and its targets offer useful prognostic markers as well as biomarkers for PI3K/AKT inhibitor efficacy in neuroblastoma. Affymetrix U133 Plus 2.0 profiling of SY5Y-TetR-FOXO3A cells treated with doxycycline and/or the PI3K/mTOR inhibitor PI-103. Each condition profiled in triplicate.

2013-05-01 | E-GEOD-42762 | biostudies-arrayexpress

Melanoma cell intrinsic GABAA receptor enhancement potentiates radiation and immune checkpoint inhibitor response by promoting direct and T cell-mediated anti-tumor activity

Project description:Most metastatic melanoma patients show variable responses to radiotherapy and do not benefit from immune checkpoint inhibitors (ICIs). Improved strategies for combination therapy that leverage potential benefits from radiotherapy and ICI are critical. Genes coding for subunits of GABAARs express functional GABAARs in melanoma cells. By enhancing GABAAR mediated anion transport, benzodiazepines depolarize melanoma cells and impair their viability. In vivo, benzodiazepine alone reduces tumor growth and potentiates radiotherapy and α-PD-L1 anti-tumor activity. Combination of benzodiazepine, radiotherapy, and α-PD-L1 results in near complete regression of treated tumors and a potent abscopal effect, mediated by increased infiltration of polyfunctional CD8+ T cells. Treated tumors show expression of cytokine:cytokine receptor interactions and overrepresentation of p53 signaling. This study identifies an anti-tumor strategy combining radiation and/or immune checkpoint inhibitor with modulation of GABAARs in melanoma using a benzodiazepine.

2020-10-23 | GSE159829 | GEO

Heterogeneity of neuroblastoma cell identity revealed by transcriptional circuitries

Project description:Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define Core Regulatory Circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed the neuroblastoma super-enhancer landscape. We discovered three types of identity in neuroblastoma cell lines: a sympathetic noradrenergic identity defined by a CRC module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs); an NCC-like identity, driven by a CRC module containing AP-1 family TFs; a mixed type further deconvoluted at the single cell level. Treatment of the mixed type with chemotherapeutic agents resulted in enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq. Functional studies demonstrated dependency of neuroblastoma with noradrenergic identity on PHOX2B, evocative of lineage addiction. Most neuroblastoma primary tumors express TFs from the noradrenergic and NCC-like modules. Our data demonstrate a novel aspect of tumor heterogeneity relevant for neuroblastoma treatment strategies.

2017-07-01 | GSE90683 | GEO

FOXO3a Is A Major Target Of Inactivation By PI3K/AKT Signaling In Aggressive Neuroblastoma

2013-05-01 | GSE42762 | GEO

Phosphoproteome and gene expression profiling of ALK inhibition in neuroblastoma cells lines reveals conserved oncogenic pathways

Project description:Neuroblastoma is a neural crest-derived embryonal tumor or the postganglionic sympathetic nervous system. Neuroblastomas show heterogeneous biologic and clinical features and , whereas a subset may undergo spontaneous differentiation or regression with little or no therapy, the majorities are difficult to cure with current modalities. The origin of these tumours remains unknown in most cases, although a number of familial cases have been associated with mutations of the ALK gene. In this study we established both phosphoproteomic and gene expression profiles of ALK activity in neuroblastoma cells exposed to first and third generation ALK TKIs, to identify the underlying molecular mechanisms and identify relevant biomarkers, signaling networks, and new therapeutic targets.

2018-11-27 | PXD011187 | Pride

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