E-GEOD-46971 - IkB-like protein NFKBIZ regulates NF-kB signaling and is critical for survival of ABC DLBCL (NFKBIZ inhibition)

Status
Released on 22 July 2013, last updated on 3 June 2014
Organism
Homo sapiens
Samples (16)
Array (1)
Protocols (7)
Description
Constitutive activation of the nuclear factor-kappa B (NF-kB) pathway is a hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). Recurrent mutations of NF-kB regulators that cause constitutive activity of this oncogenic pathway have been identified. However, it remains unclear how specific target genes are regulated. We identified the IkB-like protein NFKBIZ that binds NF-kB subunits and enhances transactivation of some NF-kB target genes while repressing others, to be upregulated in ACB compared to GCB DLBCL primary patient samples (p=5.1 x 10^-37). Knockdown of NFKBIZ by RNA interference was toxic to ABC but not GCB DLBCL cell lines. Gene expression profiling following NFKBIZ knockdown significantly downregulated a large number of NF-kB target genes, suggesting a central role in regulating NF-kB signaling. To further investigate the molecular mechanisms of how NFKBIZ mediates NF-kB signaling in ABC DLBCL, we performed immunoprecipitations and detected an interaction of NFKBIZ with both p50 and p52 NF-kB subunits, indicating that both the canonical and non-canonical NF-kB pathways are regulated by NFKBIZ. Collectively, our data imply that NFKBIZ is required for NF-kB signaling in ABC DLBCL and thus might represent a promising molecular target for future therapies. The complete dataset is comprised of three experiments with the male HBL-1 ABC DLBCL cell line: a) 8 paired GEP measurements after NFKBIZ inhibition by shRNA, b) 6 paired GEP measurements after applying the MLN inhibitor and c) 4 two-color measurements after applying a MALT inhibitor. This dataset includes 8 paired GEP measurements after NFKBIZ inhibition by shRNA.
Experiment type
transcription profiling by array 
Contacts
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-46971.idf.txt
Sample and data relationshipE-GEOD-46971.sdrf.txt
Raw data (1)E-GEOD-46971.raw.1.zip
Processed data (1)E-GEOD-46971.processed.1.zip
Array designA-GEOD-10558.adf.txt
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