Molecular Network Analyses Implicate Death-Associated Protein Kinase 3 (DAPK3) as a Key Factor in Colitis-Associated Dysplasia Progression

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dc.contributor.authorChen, Huey-Miin
dc.contributor.authorMacDonald, Justin
dc.date.accessioned2022-06-10T16:43:19Z
dc.date.available2022-06-10T16:43:19Z
dc.date.issued2022-05-23
dc.description.abstractBackground: Ulcerative colitis (UC) is a progressive disorder that elevates the risk of colon cancer development through a colitis-dysplasia-carcinoma sequence. Gene expression profiling of colitis-associated lesions obtained from patients with varied extents of UC can be mined to define molecular panels associated with colon cancer development. Methods: Differential gene expression profiles of 3 UC clinical subtypes and healthy controls were developed for the GSE47908 microarray data set of healthy controls, left-sided colitis, pancolitis, and colitis-associated dysplasia (CAD) using limma R. Results: A gene ontology enrichment analysis of differentially expressed genes (DEGs) revealed a shift in the transcriptome landscape as UC progressed from left-sided colitis to pancolitis to CAD, from being immune-centric to being cytoskeleton-dependent. Hippo signaling (via Yes-associated protein [YAP]) and Ephrin receptor signaling were the top canonical pathways progressively altered in concert with the pathogenic progression of UC. A molecular interaction network analysis of DEGs in left-sided colitis, pancolitis, and CAD revealed 1 pairwise line, or edge, that was topologically important to the network structure. This edge was found to be highly enriched in actin-based processes, and death-associated protein kinase 3 (DAPK3) was a critical member and sole protein kinase member of this network. Death-associated protein kinase 3 is a regulator of actin-cytoskeleton reorganization that controls proliferation and apoptosis. Differential correlation analyses revealed a negative correlation for DAPK3-YAP in healthy controls that flipped to positive in left-sided colitis. With UC progression to CAD, the DAPK3-YAP correlation grew progressively more positive. Conclusion: In summary, DAPK3 was identified as a candidate gene involved in UC progression to dysplasia.en_US
dc.description.grantingagencyCanadian Institutes of Health Research (CIHR)en_US
dc.identifier.citationHuey-Miin Chen, PhD, Justin A MacDonald, PhD, Molecular Network Analyses Implicate Death-Associated Protein Kinase 3 (DAPK3) as a Key Factor in Colitis-Associated Dysplasia Progression, Inflammatory Bowel Diseases, 2022;, izac098, https://doi.org/10.1093/ibd/izac098en_US
dc.identifier.doihttps://doi.org/10.1093/ibd/izac098en_US
dc.identifier.grantnumberMOP-97931en_US
dc.identifier.urihttp://hdl.handle.net/1880/114717
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.publisher.departmentBiochemistry & Molecular Biologyen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.hasversionacceptedVersionen_US
dc.publisher.institutionUniversity of Calgaryen_US
dc.publisher.policyhttps://academic.oup.com/journals/pages/open_access/funder_policiesen_US
dc.subjectcolon canceren_US
dc.subjectdeath-associated protein kinaseen_US
dc.subjectzipper-interacting protein kinaseen_US
dc.subjectdifferential-gene expressionen_US
dc.subjectulcerative colitisen_US
dc.subjectdysplasiaen_US
dc.titleMolecular Network Analyses Implicate Death-Associated Protein Kinase 3 (DAPK3) as a Key Factor in Colitis-Associated Dysplasia Progressionen_US
dc.typejournal articleen_US
ucalgary.item.requestcopytrueen_US
ucalgary.scholar.levelFacultyen_US
ucalgary.scholar.levelGraduateen_US
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