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锌指蛋白ZBTB20通过抑制FoxO1促进非小细胞肺癌中的细胞增殖。

Zinc finger protein ZBTB20 promotes cell proliferation in non-small cell lung cancer through repression of FoxO1.

作者信息

Zhao Jun-gang, Ren Kai-ming, Tang Jun

机构信息

Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China.

Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China.

出版信息

FEBS Lett. 2014 Dec 20;588(24):4536-42. doi: 10.1016/j.febslet.2014.10.005. Epub 2014 Oct 13.

Abstract

In the present study, we found that ZBTB20, a member of the POK (POZ and Krüppel) family of transcriptional repressors, was significantly up-regulated in lung cancer tissues, compared with adjacent normal tissues. Our in vitro studies further found that ZBTB20 overexpression promoted, while its inhibition using small interfering RNA suppressed cell proliferation. Consistently, key regulators in cell-cycle progression, such as Cyclin D1, Cyclin E, P21 and P27, were also regulated by ZBTB20. At the molecular level, we further revealed that FoxO1, a tumor suppressor in multiple human cancers, was transcriptionally repressed by ZBTB20. Therefore, our results highlight an important role for ZBTB20 in controlling NSCLC development, which might be helpful to identify potential therapeutic targets for its treatment.

摘要

在本研究中,我们发现转录抑制因子POK(POZ和Krüppel)家族成员ZBTB20在肺癌组织中相较于相邻正常组织显著上调。我们的体外研究进一步发现,ZBTB20的过表达促进细胞增殖,而使用小干扰RNA抑制它则会抑制细胞增殖。同样,细胞周期进程中的关键调节因子,如细胞周期蛋白D1、细胞周期蛋白E、P21和P27,也受到ZBTB20的调控。在分子水平上,我们进一步揭示,在多种人类癌症中作为肿瘤抑制因子的FoxO1受到ZBTB20的转录抑制。因此,我们的结果凸显了ZBTB20在控制非小细胞肺癌发展中的重要作用,这可能有助于识别其治疗的潜在靶点。

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