NF-κB/miR-223-3p/ARID1A axis is involved in Helicobacter pylori CagA-induced gastric carcinogenesis and progression.
NF-κB/miR-223-3p/ARID1A axis is involved in Helicobacter pylori CagA-induced gastric carcinogenesis and progression.
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NF-κB/miR-223-3p/ARID1A轴参与幽门螺杆菌CagA诱导的胃癌发生和进展
DOI：
10.1038/s41419-017-0020-9
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发表时间：
2018-01-09
影响因子：
9
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Yang F;Xu Y;Liu C;Ma C;Zou S;Xu X;Jia J;Liu Z
幽门螺杆菌(Hp)感染和由此引起的胃炎症被认为是胃癌发生和发展的最大危险因素。NF-κB在幽门螺杆菌介导的炎症与癌症的联系中起着重要作用。然而，人们对其潜在的机制知之甚少。在本研究中，我们发现幽门螺杆菌感染以Hp CagA依赖的方式诱导miR-223-3p的表达。NF-κB通过直接与miR-223-3p的启动子结合来刺激miR-223-3p的表达，并且是Hp CagA介导的miR-223-3p上调所必需的。MIR-223-3p通过直接靶向ARID1A并下调其表达，促进胃癌细胞的增殖和迁移。此外，miR-223-3p/ARID1A轴参与了CagA诱导的细胞增殖和迁移。在临床上，与相应的非癌组织相比，人胃癌组织中miR-223-3p的表达上调，而ARID1a的表达显著下调。幽门螺杆菌阳性胃癌组织中miR-223-3p的表达水平显著高于幽门螺杆菌阴性胃癌组织。此外，在胃癌组织中，miR-223-3p与ARID1A的表达呈负相关。综上所述，我们的研究结果提示，NF-κB/miR-223-3p/ARID1A轴可能将幽门螺杆菌诱导的慢性炎症过程与胃癌联系起来，从而为研究幽门螺杆菌相关性胃病的发病机制提供了新的视角。
Infection with Helicobacter pylori (H. pylori) and the resulting gastric inflammation is regarded as the strongest risk factor for gastric carcinogenesis and progression. NF-κB plays an important role in linking H. pylori-mediated inflammation to cancer. However, the underlying mechanisms are poorly understood. In this study, we find that H. pylori infection induces miR-223-3p expression in H. pylori CagA-dependent manner. NF-κB stimulates miR-223-3p expression via directly binding to the promoter of miR-223-3p and is required for H. pylori CagA-mediated upregulation of miR-223-3p. miR-223-3p promotes the proliferation and migration of gastric cancer cells by directly targeting ARID1A and decreasing its expression. Furthermore, miR-223-3p/ARID1A axis is involved in CagA-induced cell proliferation and migration. In the clinical setting, the level of miR-223-3p is upregulated, while ARID1A is downregulated significantly in human gastric cancer tissues compared with the corresponding noncancerous tissues. The expression level of miR-223-3p is significantly higher in H. pylori-positive gastric cancer tissues than that in H. pylori-negative tissues. Moreover, a negative correlation between miR-223-3p and ARID1A expression is found in the gastric cancer tissues. Taken together, our findings suggested NF-κB/miR-223-3p/ARID1A axis may link the process of H. pylori-induced chronic inflammation to gastric cancer, thereby providing a new insight into the mechanism underlying H. pylori-associated gastric diseases.
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影响因子：
7.7
作者：
Lamb, Acacia;Yang, Xiao-Dong;Chen, Lin-Feng
通讯作者：
Chen, Lin-Feng
影响因子：
24.5
作者：
Parsonnet, J;Friedman, GD;Vogelman, H
通讯作者：
Vogelman, H
影响因子：
6.4
作者：
Matsushima, Kayoko;Isomoto, Hajime;Kohno, Shigeru
通讯作者：
Kohno, Shigeru
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：
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作者：
He D;Huang C;Zhou Q;Liu D;Xiong L;Xiang H;Ma G;Zhang Z
通讯作者：
Zhang Z