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ZBTB20 通过抑制 IκBα 诱导 NF-κB 激活促进胃癌细胞迁移和侵袭。

ZBTB20 promotes cell migration and invasion of gastric cancer by inhibiting IκBα to induce NF-κB activation.

机构信息

Department of Oncology, Xuzhou Central Hospital, Xuzhou Medical University , Xuzhou , China.

Department of Medical Oncology, The First Affiliated Hospital of Soochow University , Suzhou , China.

出版信息

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3862-3872. doi: 10.1080/21691401.2019.1670188.

Abstract

Zinc finger and BTB domain containing 20 (ZBTB20), a sequence-specific transcriptional repressor, has been found to be involved in tumorigenesis. However, its role(s) in gastric cancer and the molecular mechanisms involved are poorly investigated. Here, our data demonstrated that ZBTB20 expression was markedly upregulated in gastric cancer cell lines infected with () and in gastric cancer tumor samples. Loss- and gain-of-function studies showed that ZBTB20 promoted cell proliferation, invasion and migration of gastric cancer cell lines. Mechanistically, the phosphorylation of NF-κBp65 and expression and activity of MMP-2 and MMP-9 were increased, while IκBα expression was decreased by ZBTB20 in gastric cancer cells. We further revealed that IκBα overexpression significantly inhibited NF-κB signaling as well as cell migration, invasion and proliferation in gastric cancer cell lines induced by ZBTB20 overexpression. Therefore, our findings emphasize an important role for ZBTB20 in controlling gastric cancer development, which is helpful to identify potential therapeutic targets for its treatment.

摘要

锌指和 BTB 结构域蛋白 20(ZBTB20)是一种序列特异性转录抑制剂,已被发现与肿瘤的发生有关。然而,其在胃癌中的作用及其相关的分子机制仍知之甚少。本研究结果表明,ZBTB20 在感染()的胃癌细胞系和胃癌肿瘤样本中表达显著上调。缺失和功能获得研究表明,ZBTB20 促进了胃癌细胞系的增殖、侵袭和迁移。机制上,ZBTB20 增加了 NF-κBp65 的磷酸化以及 MMP-2 和 MMP-9 的表达和活性,同时降低了 IκBα 的表达。我们进一步揭示,IκBα 的过表达显著抑制了 NF-κB 信号通路,以及由 ZBTB20 过表达诱导的胃癌细胞系的迁移、侵袭和增殖。因此,我们的研究结果强调了 ZBTB20 在控制胃癌发展中的重要作用,这有助于确定其治疗的潜在治疗靶点。

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