Research

A Role for RUNX3 in Inflammation-Induced Expression of IL23A in Gastric Epithelial Cells (Cell Reports, July 2014)

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).

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Authors:

Yit Teng Hor,1,2,4 Dominic Chih-Cheng Voon,1,4 Jason Kin Wai Koo,1 Huajing Wang,1 Wen Min Lau,1 Hassan Ashktorab,3Shing Leng Chan,1 and Yoshiaki Ito1*

1Cancer Stem Cells and Biology Programme, Cancer Science Institute of Singapore, National University of Singapore

2NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore

3Cancer Center and Gastroenterology Division, Department of Medicine, Howard University Hospital, 2041 Georgia Avenue N.W., Washington, DC 20060, USA

4Co-first author

*Correspondence: csiitoy[at]nus.edu.sg