JMJD2B is required for Helicobacter pylori-induced gastric carcinogenesis via regulating COX-2 expression.
JMJD2B is required for Helicobacter pylori-induced gastric carcinogenesis via regulating COX-2 expression.
复制标题
JMJD2B是幽门螺杆菌通过调节COX-2表达诱导胃癌发生所必需的
DOI：
10.18632/oncotarget.9573
复制
发表时间：
2016-06-21
期刊：
影响因子：
--
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Han F;Ren J;Zhang J;Sun Y;Ma F;Liu Z;Yu H;Jia J;Li W
幽门螺杆菌（h.p ylori）感染是胃癌发生和发展的最强危险因素。然而，幽门螺杆菌诱导的发病机制尚不清楚。在这项研究中，我们探讨了幽门螺杆菌感染在JMJD2B上调中的作用以及胃癌发生的机制。我们发现JMJD2B可以通过β-catenin途径被幽门螺杆菌感染诱导。在幽门螺杆菌感染后，β-catenin直接结合JMJD2B启动子，刺激JMJD2B的表达。增加的JMJD2B与NF-κB结合到COX-2启动子上，通过局部去甲基化H3K9me3来增强其转录。幽门螺杆菌感染小鼠体内JMJD2B和COX-2表达上调。从胃炎到胃癌，人胃组织中JMJD2B和COX-2的表达逐渐升高。幽门螺杆菌阳性胃炎组织中JMJD2B和COX-2水平明显高于幽门螺杆菌阴性组织。此外，JMJD2B与COX-2在胃炎和胃癌组织中的表达均呈正相关。因此，JMJD2B是触发幽门螺杆菌诱导的慢性炎症和胃癌发生进展的关键因素，可能成为干预胃癌的新靶点。
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.
登录
查看更多内容
DOI：
10.1152/ajplung.00338.2003
发表时间：
2004-05-01
影响因子：
4.9
作者：
Park, GY;Joo, M;Christman, JW
通讯作者：
Christman, JW
影响因子：
3.3
作者：
Tatsuguchi, A;Matsui, K;Sakamoto, C
通讯作者：
Sakamoto, C
DOI：
10.1086/596660
发表时间：
2009-03-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Nagy TA;Frey MR;Yan F;Israel DA;Polk DB;Peek RM Jr
通讯作者：
Peek RM Jr
影响因子：
3.7
作者：
Ding SZ;Fischer W;Kaparakis-Liaskos M;Liechti G;Merrell DS;Grant PA;Ferrero RL;Crowe SE;Haas R;Hatakeyama M;Goldberg JB
通讯作者：
Goldberg JB
影响因子：
37.3
作者：
Gnad T;Feoktistova M;Leverkus M;Lendeckel U;Naumann M
通讯作者：
Naumann M