Histone demethylase RBP2 induced by Helicobactor Pylori CagA participates in the malignant transformation of gastric epithelial cells.
Histone demethylase RBP2 induced by Helicobactor Pylori CagA participates in the malignant transformation of gastric epithelial cells.
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幽门螺杆菌CagA诱导的组蛋白去甲基化酶RBP2参与胃上皮细胞恶性转化
DOI：
10.18632/oncotarget.2185
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发表时间：
2014-07-30
期刊：
影响因子：
--
通讯作者：
Jia J
中科院分区：
文献类型：
--
作者：
Liang X;Zeng J;Wang L;Shen L;Li S;Ma L;Ci X;Yu J;Jia M;Sun Y;Liu Z;Liu S;Li W;Yu H;Chen C;Jia J
幽门螺杆菌诱导的胃上皮细胞恶性转化有助于肿瘤的发展，但其潜在机制尚不清楚。在这里，我们证明了RBP2，一种新发现的组蛋白去甲基化酶，可以通过PI3K/AKT- sp1途径被CagA诱导，依赖于AKT磷酸化。Sp1直接与RBP2启动子结合并增强其表达，上调后的RBP2显著增加Cyclin D1转录，促进胃上皮细胞恶性转化。进一步的数据表明，内源性RBP2的敲低在体外和体内均能显著抑制胃癌（GC）的发展。综上所述，CagA- PI3K/AKT-Sp1-RBP2-Cyclin D1通路可能是胃上皮细胞恶性转化进而胃癌（GC）的新机制。因此，RBP2可能将慢性炎症与肿瘤发展联系起来，其抑制可能具有潜在的治疗优势。
Gastric epithelial cell malignant transformation induced by Helicobactor Pylori contributes to tumor development, but the underlying mechanisms for this remain unclear. Here we demonstrate that RBP2, a newly identified histone demethylase, can be induced by CagA via PI3K/AKT-Sp1 pathway depending on AKT phosphorylation. Sp1 directly binds to RBP2 promoter and enhances its expression then the upregulated RBP2 significantly increases Cyclin D1 transcription, which contributes to gastric epithelial cell malignant transformation. Further data indicate that knockdown of endogenous RBP2 dominantly inhibits gastric cancer (GC) development both in vitro and in vivo. In conclusion, this CagA- PI3K/AKT-Sp1-RBP2-Cyclin D1 pathway may serve as a novel mechanism for gastric epithelial cell malignant transformation and then gastric cancer (GC). Therefore, RBP2 may link chronic inflammation to tumor development and its inhibition may have potential therapeutic advantages.