Journal
ONCOTARGET
Volume 7, Issue 25, Pages 38626-38637Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.9573
Keywords
JMJD2B; KDM4B; Helicobacter pylori; COX-2; gastric cancer
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Funding
- National Basic Research Program of China (973 Program) [2012CB911202]
- National Natural Science Foundation of China [81372680, 81371781, 81402108, 81471991, 81571960]
- Science Foundation for outstanding young scientists of Shandong Province [BS2014SW015]
- China Postdoctoral Science Foundation [2014M551915]
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Helicobacter pylori (H. pylori) infection is the strongest risk factor for the initiation and progression of gastric cancer. However, the mechanism of H. pylori-induced pathogenesis remains unclear. In this study, we investigate the role of H. pylori infection in JMJD2B upregulation and the mechanism underlying gastric carcinogenesis. We find that JMJD2B can be induced by H. pylori infection via beta-catenin pathway. beta-catenin directly binds to JMJD2B promoter and stimulates JMJD2B expression following H. pylori infection. Increased JMJD2B, together with NF-kappa B, binds to COX-2 promoter to enhance its transcription by demethylating H3K9me3 locally. JMJD2B and COX-2 expression is upregulated in H. pylori infected mice in vivo. Furthermore, JMJD2B and COX-2 expression is gradually increased in human gastric tissues from gastritis to gastric cancer. The level of JMJD2B and COX-2 in H. pylori-positive gastritis tissues is significantly higher than that in H. pylori-negative tissues. Moreover, a positive correlation between JMJD2B and COX-2 expression is found in both gastritis and gastric cancer tissues. Therefore, JMJD2B is a crucial factor in triggering H. pylori-induced chronic inflammation and progression of gastric carcinogenesis and it may serve as a novel target for the intervention of gastric cancer.
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