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Title: Targeting Myc signaling pathway by inhibition of histone demethylase JMJD2B (ciclopirox)      
dateReleased:
01-01-2014
description:
Epigenetic alterations appear to modulate Myc signaling. We investigated the role of the histone demethylase JMJD2B in Myc-mediated neuroblastoma pathogenesis. We demonstrate that Myc physically interacts with and recruits this epigenetic modifier, which removes repressive H3K9 methyl marks from Myc-target genes. JMJD2B regulates neuroblastoma proliferation and, together with MYCN amplification, identifies a subgroup of poor prognosis patients. We identify a novel histone demethylase inhibitor, ciclopirox, which targets JMJD2B and, consequently, Myc signaling, thereby inhibiting neuroblastoma proliferation and inducing differentiation. In xenograft studies, genetic and pharmacologic inhibition of JMJD2B resulted in significant tumor growth restriction. Our findings provide insight into epigenetic regulation of Myc via histone methylation and proof-of-concept for pharmacologic inhibition of histone demethylases to target Myc signaling in cancer. 8 samples were treated with vehicle or ciclopirox.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-45969
refinement:
raw
alternateIdentifiers:
45969
keywords:
functional genomics
dateModified:
06-03-2014
availability:
available
types:
gene expression
name:
Homo sapiens
ID:
A-GEOD-13158
name:
[HT_HG-U133_Plus_PM] Affymetrix HT HG-U133+ PM Array Plate
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-45969/E-GEOD-45969.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-45969/E-GEOD-45969.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45969
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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