title: A role for RUNX3 in inflammation-induced expression of IL23A in gastric epithelial cells.
abstract: RUNX3 functions as a tumor suppressor in the gastric epithelium, where its inactivation is frequently observed during carcinogenesis. We identified IL23A as a RUNX3 target gene in gastric epithelial cells. This was confirmed in a series of in vitro analyses in gastric epithelial cell lines. In elucidating the underlying regulatory network, we uncovered a prominent role for the TNF-α/NF-κB pathway in activating IL23A transcription. Moreover, the activating effect of TNF-α was markedly augmented by the infection of Helicobacter pylori, the primary cause of human gastritis. Of note, H. pylori utilized the CagA/SHP2 pathway to activate IL23A, as well as the induction of the NOD1 pathway by iE-DAP. Importantly, RUNX3 synergized strongly with these physiologically relevant stimuli to induce IL23A. Lastly, we present evidence for the secretion of IL23A by gastric epithelial cells in a form that is distinct from canonical IL-23 (IL23A/IL12B).
authors.affiliation: Cancer Stem Cells and Biology Programme, Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456, Singapore.
authors.forename: Yit Teng
authors.initials: YT
authors.lastname: Hor
authors.affiliation: Cancer Stem Cells and Biology Programme, Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
authors.forename: Dominic Chih-Cheng
authors.initials: DC
authors.lastname: Voon
authors.affiliation: Cancer Stem Cells and Biology Programme, Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
authors.forename: Jason Kin Wai
authors.initials: JK
authors.lastname: Koo
authors.affiliation: Cancer Stem Cells and Biology Programme, Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
authors.forename: Huajing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Cancer Stem Cells and Biology Programme, Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
authors.forename: Wen Min
authors.initials: WM
authors.lastname: Lau
authors.affiliation: Cancer Center and Gastroenterology Division, Department of Medicine, Howard University Hospital, 2041 Georgia Avenue N.W., Washington, DC 20060, USA.
authors.forename: Hassan
authors.initials: H
authors.lastname: Ashktorab
authors.affiliation: Cancer Stem Cells and Biology Programme, Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore.
authors.forename: Shing Leng
authors.initials: SL
authors.lastname: Chan
authors.affiliation: Cancer Stem Cells and Biology Programme, Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore. Electronic address: csiitoy@nus.edu.sg.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000942:Antigens, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology; D016480:Helicobacter pylori / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology; D053760:Interleukin-23 Subunit p19 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D050677:Core Binding Factor Alpha 3 Subunit; C508840:IL23A protein, human; D053760:Interleukin-23 Subunit p19; D016328:NF-kappa B; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; C493729:Runx3 protein, human; D014409:Tumor Necrosis Factor-alpha; C080866:cagA protein, Helicobacter pylori; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11