Gene Set: CERVERA_SDHB_TARGETS_1_UP

Standard name CERVERA_SDHB_TARGETS_1_UP
Systematic name M15549
Brief description Genes turned on in Hep3B cells (hepatocellular carcinoma, HCC) upon knockdown of SDHB [GeneID=6390] by RNAi.
Full description or abstract Recently, enzymes of the tricarboxylic acid (TCA) cycle have emerged as novel tumor suppressors. In particular, mutations in the nuclear-encoded subunits of succinate dehydrogenase (SDHB, SDHC, and SDHD) cause paragangliomas and pheochromocytomas. Although the mechanism(s) by which disruption of mitochondrial metabolism leads to neoplasia is largely unknown, increasing evidence points to an activation of pseudohypoxia. In this study, we have shown that silencing of SDHB using DNA-based small interfering RNA resulted in major impairments in cellular proliferation, respiration, and a corresponding shift to glycolysis. The levels of reactive oxygen species, however, were unchanged. As expected, hypoxia-inducible factor-1 alpha (HIF-1 alpha) and HIF-2alpha were up-regulated in chronically silenced cells, suggesting that a pseudohypoxic state was attained. In addition, the c-Jun amino-terminal kinase and p38 kinase stress signaling proteins were hyperphosphorylated in SDHB-silenced cells. Microarray analysis showed that >400 genes were influenced (6-fold or more up-regulation or down-regulation) by silencing of SDHB, confirming the importance of the TCA cycle in cellular metabolism. Examples of dysregulated genes included those involved in proliferation, adhesion, and the hypoxia pathway. Of interest, SDHB-silenced cells had a greater capacity to adhere to extracellular matrix components, including fibronectin and laminin, than control cells, thus suggesting a possible mechanism of tumor initiation. Although transient silencing of the HIF-1 alpha transcription factor in SDHB-silenced cells had little effect on the expression of a subset of up-regulated genes, it partially reversed the adhesion phenotype to fibronectin, pointing to a potentially important role for HIF-1 in this process.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18519664   Authors: Cervera AM,Apostolova N,Crespo FL,Mata M,McCreath KJ
Exact source Table 2AS
Related gene sets (show 2 additional gene sets from the source publication)
External links  
Filtered by similarity
Organism Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform AFFY_HG_U133
Dataset references (show 1 datasets)
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps (show collections to investigate for overlap with this gene set)
Compendia expression profiles GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 121 genes
Gene families Categorize these 121 genes by gene family
Show members (show 143 members mapped to 121 genes)
Version history 3.0: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.