Gene Set: WOTTON_RUNX_TARGETS_DN

Standard name WOTTON_RUNX_TARGETS_DN
Systematic name M4303
Brief description Common target genes down-regulated by all three Runx family members (RUNX1, RUNX2, and RUNX3 [GeneID=861;860;864]) in MEF cells (embryonic fibroblasts).
Full description or abstract The Runx genes are important in development and cancer, where they can act either as oncogenes or tumour suppressors. We compared the effects of ectopic Runx expression in established fibroblasts, where all three genes produce an indistinguishable phenotype entailing epithelioid morphology and increased cell survival under stress conditions. Gene array analysis revealed a strongly overlapping transcriptional signature, with no examples of opposing regulation of the same target gene. A common set of 50 highly regulated genes was identified after further filtering on regulation by inducible RUNX1-ER. This set revealed a strong bias toward genes with annotated roles in cancer and development, and a preponderance of targets encoding extracellular or surface proteins, reflecting the marked effects of Runx on cell adhesion. Furthermore, in silico prediction of resistance to glucocorticoid growth inhibition was confirmed in fibroblasts and lymphoid cells expressing ectopic Runx. The effects of fibroblast expression of common RUNX1 fusion oncoproteins (RUNX1-ETO, TEL-RUNX1 and CBFB-MYH11) were also tested. Although two direct Runx activation target genes were repressed (Ncam1 and Rgc32), the fusion proteins appeared to disrupt the regulation of downregulated targets (Cebpd, Id2 and Rgs2) rather than impose constitutive repression. These results elucidate the oncogenic potential of the Runx family and reveal novel targets for therapeutic inhibition.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18560354   Authors: Wotton S,Terry A,Kilbey A,Jenkins A,Herzyk P,Cameron E,Neil JC
Exact source Table 1
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Organism Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform AFFY_Mouse430
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Version history 3.0: First introduced

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