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 Helicobacter pylori (H. pylori) 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.

中文翻译：

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ZBTB20通过抑制IκBα诱导NF-κB活化来促进胃癌的细胞迁移和侵袭。

锌指和包含20的BTB结构域（ZBTB20）是一种序列特异性转录阻遏物，已被发现与肿瘤发生有关。然而，对其在胃癌中的作用和涉及的分子机制的研究很少。在这里，我们的数据表明ZBTB20表达在幽门螺杆菌（H. pylori）感染的胃癌细胞系和胃癌肿瘤样品中明显上调。功能丧失和功能增强研究表明ZBTB20促进胃癌细胞系的细胞增殖，侵袭和迁移。从机制上讲，ZBTB20在胃癌细胞中增加了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过表达显着抑制ZBTB20过表达诱导的胃癌细胞系中的NF-κB信号传导以及细胞迁移，侵袭和增殖。因此，我们的发现强调了ZBTB20在控制胃癌发展中的重要作用，这有助于确定潜在的治疗靶点。