Negative regulation of the IFN/STAT signaling pathway by the Trim24 tumor suppressor protein through Rara inhibition
Transcriptomics Dataset
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General Information
AccessionGSE19675
TitleNegative regulation of the IFN/STAT signaling pathway by the Trim24 tumor suppressor protein through Rara inhibition
DescriptionRecent genetic studies in mice have established a key role for the nuclear receptor coregulator Trim24 in liver tumor suppression and provided evidence that Trim24 suppresses hepatocarcinogenesis by inhibiting retinoic acid receptor alpha (Rara)-dependent transcription and cell proliferation. However, it is unknown which downstream targets of Rara regulated by Trim24 are critical for tumorigenesis. We report here that loss of Trim24 results in the overexpression of interferon (IFN)/STAT pathway genes in the liver, a process that occurs early in tumorigenesis and is more pronounced in tumors, despite the enhanced expression, late in the disease, of negative regulators such as Usp18, Socs1 and Socs2. Remarkably, Rara haplodeficiency, which was previously shown to suppress tumor development in Trim24-/- mice, also suppresses overexpression of the IFN/STAT pathway, thus providing evidence for a cross-pathway control that may be relevant to the transformation process. Biochemical studies revealed that Trim24 binds to the retinoic acid (RA)-responsive element in the Stat1 promoter in a RA-dependent manner and represses RA-induced transcription from this promoter. Together, these results identify Trim24 as a novel regulator of the IFN/STAT pathway and indicate that Trim24-mediated repression of the IFN/STAT signaling through Rara inhibition may play a critical role in preventing liver cancer.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19675
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Keyword
Dataset Accession
Enrichr
Published May 2016
A comprehensive gene set enrichment analysis web server 2016 update
7759
65
Characteristic Direction
Published March 2014
A geometrical multivariate approach to identify differentially expressed genes
26829
GeneMANIA
Published June 2010
Biological network integration for gene prioritization and predicting gene function
7435
L1000CDS2
Published August 2016
An ultra-fast LINCS L1000 Characteristic Direction signature search engine
7756
PAEA
Published November 2015
Enrichment analysis tool implementing the principal angle method
3879
Canned Analyses generated with the dataset
Filters  
Dataset Accession
Tool Name
Direction
Geneset
Small molecules which mimic TRIM24 knockout
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse TRIM24 knockout
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in TRIM24 knockout
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Interaction network and enrichment analysis of genes downregulated in TRIM24 knockout
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in TRIM24 knockout
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Enrichment analysis of genes downregulated in TRIM24 knockout
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most downregulated genes identified by...
Enrichment analysis of genes upregulated in TRIM24 knockout
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most upregulated genes identified by a...
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