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.
Highlights
Gastric cancer is the fifth most common malignancies and the third leading cause of cancer-related death among all cancers worldwide
Given the role of H. pylori infection in gastric malignant transformation, we investigate the link between H. pylori infection and JMJD2B expression associated with gastric cancer pathogenesis
These findings demonstrated that H. pylori induced JMJD2B upregulation at transcriptional level
Summary
Gastric cancer is the fifth most common malignancies and the third leading cause of cancer-related death among all cancers worldwide. According to the global cancer statistics in 2012, an estimated 951,600 new stomach cancer cases and 723,100 deaths occurred [1]. Since it is lack of reliable early diagnostic markers, most patients are diagnosed at the advanced or metastatic stage. H. pylori infection and the resulting gastric inflammation is the strongest identified risk factor for the development of gastric cancer [3]. JMJD2B is overexpressed in gastric cancer and plays a role in tumor cell proliferation, survival, invasion and metastasis [13, 14]. Given the role of H. pylori infection in gastric malignant transformation, we investigate the link between H. pylori infection and JMJD2B expression associated with gastric cancer pathogenesis
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