FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2320565333> ?p ?o ?g. }

• W2320565333 endingPage "A14" @default.
• W2320565333 startingPage "A13.3" @default.
• W2320565333 abstract "<h3>Introduction</h3> The prognosis of oesophageal cancer remains poor with < 10% 5-year survival. Delineating the molecular pathogenesis of oesophageal cancer could inform future research into targeted therapies and may uncover novel biomarkers to aid management decisions. As a transcription factor with important roles in the control of cell cycle transcription, FOXM1 regulates cellular proliferation and chromosome stability. FOXM1 is frequently overexpressed in human cancers and this aberrant expression has been implicated in cancer initiation, progression and resistance to chemotherapy. Overexpression of FOXM1 mRNA and protein has recently been described in oesophageal adenocarcinoma (OAC) tissues. We aim to identify novel gene targets of FOXM1 to better understand the molecular pathogenesis of OAC. <h3>Methods</h3> Chromatin immunoprecipitation (ChIP) followed by deep sequencing (ChIP-seq) of FOXM1 binding sites was performed in OE33 OAC cells. FOXM1 binding at target gene promoters was confirmed with ChIP-qPCR studies. Target gene expression in OE33 cells after siRNA-mediated FOXM1 depletion was examined using qRT-PCR and western blotting. Target gene expression in OAC tissues was examined by analysis of microarray gene expression data. Statistical significance (<i>p</i>)in knockdown studies was calculated by Student’s <i>t</i>-test. The Pearson correlation coefficient (r) was used to measure strength of correlation of gene expression. <h3>Results</h3> Putative novel FOXM1 targets identified from an existing FOXM1 ChIP-seq dataset in U2OS osteosarcoma cells were validated by ChIP-seq in OE33 cells. A large overlap between the genes bound by FOXM1 in both cell types was observed. Genes with FOXM1 binding in both cell types whose expression was highly correlated with FOXM1 in OAC tissues such as <i>ETV4</i>, <i>SKA2</i> and <i>NUCKS1</i> (r = 0.83, 0.84 and 0.72) were analysed further with ChIP-qPCR and FOXM1 knockdown gene expression studies. OE33 cells demonstrated significant FOXM1 binding at the <i>ETV4</i> promoter and a reduction in <i>ETV4</i> mRNA in FOXM1 depleted cells was observed compared to control (<i>p</i> = 0.0006). However, despite highly significant FOXM1 binding at the <i>SKA2</i> and <i>NUCKS1</i> promoters the reduction in <i>SKA2</i>/<i>NUCKS1</i> mRNA following FOXM1 knockdown was modest and not significant. <h3>Conclusion</h3> We have identified <i>ETV4</i> as a novel FOXM1 target in oesophageal cancer. We found strong correlation with FOXM1 expression in clinical tissues, <i>in vivo</i> FOXM1 binding to its regulatory regions and evidence of regulation by FOXM1 in OE33 cells. Our studies also highlight the importance of validating ChIP-seq data with gene expression analysis since transcription factor binding at gene promoters does not always correlate with transcriptional regulation by that transcription factor. <h3>Disclosure of Interest</h3> None Declared" @default.
• W2320565333 created "2016-06-24" @default.
• W2320565333 creator A5000900863 @default.
• W2320565333 creator A5026378420 @default.
• W2320565333 creator A5075599545 @default.
• W2320565333 creator A5087669313 @default.
• W2320565333 date "2013-06-01" @default.
• W2320565333 modified "2023-09-27" @default.
• W2320565333 title "OC-031 Using Genome-Wide Studies to Identify Novel Foxm1 Transcription Factor Target Genes in Oesophageal Cancer" @default.
• W2320565333 doi "https://doi.org/10.1136/gutjnl-2013-304907.031" @default.
• W2320565333 hasPublicationYear "2013" @default.
• W2320565333 type Work @default.
• W2320565333 sameAs 2320565333 @default.
• W2320565333 citedByCount "0" @default.
• W2320565333 crossrefType "journal-article" @default.
• W2320565333 hasAuthorship W2320565333A5000900863 @default.
• W2320565333 hasAuthorship W2320565333A5026378420 @default.
• W2320565333 hasAuthorship W2320565333A5075599545 @default.
• W2320565333 hasAuthorship W2320565333A5087669313 @default.
• W2320565333 hasBestOaLocation W23205653331 @default.
• W2320565333 hasConcept C101762097 @default.
• W2320565333 hasConcept C104317684 @default.
• W2320565333 hasConcept C134320426 @default.
• W2320565333 hasConcept C150194340 @default.
• W2320565333 hasConcept C170240278 @default.
• W2320565333 hasConcept C173396325 @default.
• W2320565333 hasConcept C502942594 @default.
• W2320565333 hasConcept C54355233 @default.
• W2320565333 hasConcept C86339819 @default.
• W2320565333 hasConcept C86803240 @default.
• W2320565333 hasConceptScore W2320565333C101762097 @default.
• W2320565333 hasConceptScore W2320565333C104317684 @default.
• W2320565333 hasConceptScore W2320565333C134320426 @default.
• W2320565333 hasConceptScore W2320565333C150194340 @default.
• W2320565333 hasConceptScore W2320565333C170240278 @default.
• W2320565333 hasConceptScore W2320565333C173396325 @default.
• W2320565333 hasConceptScore W2320565333C502942594 @default.
• W2320565333 hasConceptScore W2320565333C54355233 @default.
• W2320565333 hasConceptScore W2320565333C86339819 @default.
• W2320565333 hasConceptScore W2320565333C86803240 @default.
• W2320565333 hasIssue "Suppl 1" @default.
• W2320565333 hasLocation W23205653331 @default.
• W2320565333 hasOpenAccess W2320565333 @default.
• W2320565333 hasPrimaryLocation W23205653331 @default.
• W2320565333 hasRelatedWork W2039352901 @default.
• W2320565333 hasRelatedWork W2110085982 @default.
• W2320565333 hasRelatedWork W2163569233 @default.
• W2320565333 hasRelatedWork W2783802064 @default.
• W2320565333 hasRelatedWork W4205863609 @default.
• W2320565333 hasRelatedWork W4296941420 @default.
• W2320565333 hasRelatedWork W4318460031 @default.
• W2320565333 hasRelatedWork W4320489372 @default.
• W2320565333 hasRelatedWork W4361254661 @default.
• W2320565333 hasRelatedWork W4361254676 @default.
• W2320565333 hasVolume "62" @default.
• W2320565333 isParatext "false" @default.
• W2320565333 isRetracted "false" @default.
• W2320565333 magId "2320565333" @default.
• W2320565333 workType "article" @default.