Gene Set: KRIEG_HYPOXIA_NOT_VIA_KDM3A

Standard name KRIEG_HYPOXIA_NOT_VIA_KDM3A
Systematic name M2469
Brief description Genes induced under hypoxia independently of KDM3A [GeneID=55818] in RCC4 cells (renal carcinoma) expressing VHL [GeneID=7428].
Full description or abstract The hypoxia-inducible transcription factors (HIFs) directly and indirectly mediate cellular adaptation to reduced oxygen tensions. Recent studies have shown that the histone demethylase genes JMJD1A, JMJD2B, and JARID1B are HIF targets, suggesting that HIFs indirectly influence gene expression at the level of histone methylation under hypoxia. In this study, we identify a subset of hypoxia-inducible genes that are dependent on JMJD1A in both renal cell and colon carcinoma cell lines. JMJD1A regulates the expression of adrenomedullin (ADM) and growth and differentiation factor 15 (GDF15) under hypoxia by decreasing promoter histone methylation. In addition, we demonstrate that loss of JMJD1A is sufficient to reduce tumor growth in vivo, demonstrating that histone demethylation plays a significant role in modulating growth within the tumor microenvironment. Thus, hypoxic regulation of JMJD1A acts as a signal amplifier to facilitate hypoxic gene expression, ultimately enhancing tumor growth.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 19858293   Authors: Krieg AJ,Rankin EB,Chan D,Razorenova O,Fernandez S,Giaccia AJ
Exact source Table 2S: list 3
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(show 2 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Arthur Liberzon (Broad Institute)
Source platform EntrezGeneIds
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.1: First introduced

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