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ZNF280A 通过调控 EIF3C 的表达促进肺腺癌的发展。

ZNF280A promotes lung adenocarcinoma development by regulating the expression of EIF3C.

机构信息

Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing, China.

Department of Medical Oncology, Peking Union Medical College Hospital, Beijing, China.

出版信息

Cell Death Dis. 2021 Jan 4;12(1):39. doi: 10.1038/s41419-020-03309-9.

Abstract

Lung adenocarcinoma (LUAD) is the most common histological subtype in non-small cell lung cancer, which is the malignant tumor with the highest mortality and morbidity in the world. Herein, ZNF280A, a member of the zinc finger protein family carrying two consecutive Cys2His2 zinc finger domains, was shown by us to act as a tumor driver in LUAD. The immunohistochemical analysis of ZNF280A in LUAD indicated its positive correlation with tumor grade, pathological stage and lymphatic metastasis, and negative relationship with patients' survival. A loss-of-function study revealed the inhibition of LUAD development by ZNF280A in vitro and in vivo, whereas ZNF280A overexpression induced opposite effects. Statistical analysis of gene expression profiling in LUAD cells with or without ZNF280A knockdown identified EIF3C as a potential downstream of ZNF280A, which possesses similar regulatory effects on phenotypes of LUAD cells with ZNF280A. Moreover, downregulation of EIF3C in ZNF280A-overexpressed cells could attenuate neutralize the ZNF280A-induced promotion of LUAD. In summary, our study demonstrated that ZNF280A may promote the development of LUAD by regulating cell proliferation, apoptosis, cell cycle, and cell migration and probably via interacting EIF3C.

摘要

肺腺癌(LUAD)是非小细胞肺癌中最常见的组织学亚型,是世界上死亡率和发病率最高的恶性肿瘤。在此,我们发现锌指蛋白家族的成员 ZNF280A 作为 LUAD 的肿瘤驱动因子发挥作用,它携带两个连续的 Cys2His2 锌指结构域。对 LUAD 中 ZNF280A 的免疫组织化学分析表明,其与肿瘤分级、病理分期和淋巴转移呈正相关,与患者的生存呈负相关。功能丧失研究表明 ZNF280A 在体外和体内抑制 LUAD 的发展,而 ZNF280A 过表达则诱导相反的效果。对 ZNF280A 敲低或不敲低的 LUAD 细胞的基因表达谱进行统计分析,确定 EIF3C 是 ZNF280A 的一个潜在下游基因,对 LUAD 细胞表型具有类似的调节作用。此外,在 ZNF280A 过表达细胞中下调 EIF3C 可以减弱中和 ZNF280A 诱导的 LUAD 促进作用。综上所述,我们的研究表明,ZNF280A 可能通过调节细胞增殖、凋亡、细胞周期和细胞迁移来促进 LUAD 的发展,可能通过与 EIF3C 相互作用来实现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e164/7791122/793719f7e34a/41419_2020_3309_Fig1_HTML.jpg

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