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Oncotarget. 2016 Jun 21;7(25):38626-38637. doi: 10.18632/oncotarget.9573.

JMJD2B is required for Helicobacter pylori-induced gastric carcinogenesis via regulating COX-2 expression.

Author information

1
Department of Microbiology, Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
2
Department of Urology, Qilu Hospital, Shandong University, Jinan, PR China.
3
Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, PR China.

Abstract

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 β-catenin pathway. β-catenin directly binds to JMJD2B promoter and stimulates JMJD2B expression following H. pylori infection. Increased JMJD2B, together with NF-κB, 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.

KEYWORDS:

COX-2; Helicobacter pylori; JMJD2B; KDM4B; gastric cancer

PMID:
27232941
PMCID:
PMC5122416
DOI:
10.18632/oncotarget.9573
[Indexed for MEDLINE]
Free PMC Article

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