title: JMJD2B is required for Helicobacter pylori-induced gastric carcinogenesis via regulating COX-2 expression.
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.
authors.affiliation: Department of Microbiology, Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Fengjuan
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of Microbiology, Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.|Department of Urology, Qilu Hospital, Shandong University, Jinan, PR China.
authors.forename: Juchao
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Microbiology, Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Yundong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Microbiology, Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Ma
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Microbiology, Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Han
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Microbiology, Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Jihui
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Microbiology, Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D016481:Helicobacter Infections / Q000201:enzymology* / Q000473:pathology; D016480:Helicobacter pylori / Q000302:isolation & purification*; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000382:microbiology* / Q000473:pathology; D014162:Transfection
chemical_list: D056484:Jumonji Domain-Containing Histone Demethylases; C523637:KDM4B protein, human; C511781:Kdm4b protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: COX-2; Helicobacter pylori; JMJD2B; KDM4B; gastric cancer