Identification of PBX1 Target Genes in Cancer Cells by Global Mapping of PBX1 Binding Sites

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dc.contributor.authorThiaville, Michelle M.en
dc.contributor.authorStoeck, Alexanderen
dc.contributor.authorChen, Lien
dc.contributor.authorWu, Ren-Chinen
dc.contributor.authorMagnani, Lucaen
dc.contributor.authorOidtman, Jessicaen
dc.contributor.authorShih, Ie-Mingen
dc.contributor.authorLupien, Mathieuen
dc.contributor.authorWang, Tian-Lien
dc.contributor.departmentElectrical and Computer Engineeringen
dc.date.accessioned2018-10-29T13:47:23Zen
dc.date.available2018-10-29T13:47:23Zen
dc.date.issued2012-05-02en
dc.description.abstractPBX1 is a TALE homeodomain transcription factor involved in organogenesis and tumorigenesis. Although it has been shown that ovarian, breast, and melanoma cancer cells depend on PBX1 for cell growth and survival, the molecular mechanism of how PBX1 promotes tumorigenesis remains unclear. Here, we applied an integrated approach by overlapping PBX1 ChIP-chip targets with the PBX1-regulated transcriptome in ovarian cancer cells to identify genes whose transcription was directly regulated by PBX1. We further determined if PBX1 target genes identified in ovarian cancer cells were co-overexpressed with PBX1 in carcinoma tissues. By analyzing TCGA gene expression microarray datasets from ovarian serous carcinomas, we found co-upregulation of PBX1 and a significant number of its direct target genes. Among the PBX1 target genes, a homeodomain protein MEOX1 whose DNA binding motif was enriched in PBX1-immunoprecipicated DNA sequences was selected for functional analysis. We demonstrated that MEOX1 protein interacts with PBX1 protein and inhibition of MEOX1 yields a similar growth inhibitory phenotype as PBX1 suppression. Furthermore, ectopically expressed MEOX1 functionally rescued the PBX1-withdrawn effect, suggesting MEOX1 mediates the cellular growth signal of PBX1. These results demonstrate that MEOX1 is a critical target gene and cofactor of PBX1 in ovarian cancers.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0036054en
dc.identifier.eissn1932-6203en
dc.identifier.issue5en
dc.identifier.othere36054en
dc.identifier.pmid22567123en
dc.identifier.urihttp://hdl.handle.net/10919/85577en
dc.identifier.volume7en
dc.language.isoenen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleIdentification of PBX1 Target Genes in Cancer Cells by Global Mapping of PBX1 Binding Sitesen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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