Tristetraprolin inhibits gastric cancer progression through suppression of IL-33.
Tristetraprolin inhibits gastric cancer progression through suppression of IL-33.
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DOI：
10.1038/srep24505
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发表时间：
2016-04-14
影响因子：
4.6
通讯作者：
Xia J
中科院分区：
文献类型：
--
作者：
Deng K;Wang H;Shan T;Chen Y;Zhou H;Zhao Q;Xia J
Tristetraprolin（TTP）是一种腺嘌呤/尿苷（Au）富集元件（ARE）结合蛋白，可诱导mRNA降解。在这项研究中，我们报告，TTP抑制白细胞介素-33（IL-33），一种肿瘤促进炎性细胞因子的表达，从而抑制胃癌（GC）的进展。TTP的过表达降低了IL-33的水平，而TTP的敲低增加了IL-33的水平。我们还发现TTP通过调节IL-33抑制GC细胞系的增殖、迁移和侵袭。胃癌组织中TTP RNA和蛋白水平明显降低，与IL-33水平呈负相关，并与胃癌浸润深度、淋巴结转移、TNM分期及生存率密切相关。综上所述，这些发现将TTP鉴定为IL-33的下调因子，并进一步表明TTP可以作为诊断GC的新生物标志物和作为GC治疗的潜在治疗靶点。
Tristetraprolin (TTP) is an adenine/uridine (AU)-rich element (ARE)-binding protein that can induce degradation of mRNAs. In this study, we report that TTP suppresses the expression of interleukin-33 (IL-33), a tumor-promoting inflammatory cytokine, and thereby inhibits the progression of gastric cancer (GC). Overexpression of TTP decreased the level of IL-33, whereas knockdown of TTP increased IL-33 levels. We also discovered that TTP inhibited the proliferation, migration, and invasion of GC cell lines through regulation of IL-33. Furthermore, TTP RNA and protein levels were remarkably reduced in GC and inversely correlated with IL-33 level, and they were also closely associated with depth of invasion, lymph node metastasis, advanced TNM stage, as well as survival rate. Taken together, these findings identified TTP as a downregulator of IL-33, and further suggest that TTP can serve as a novel biomarker for the diagnosis of GC and as a potential therapeutic target for GC treatment.