TRIM21 Inhibits the Proliferation and Migration of Lung Adenocarcinoma Cells by Interacting with ZSWIM1

TL;DR

This study shows that TRIM21 inhibits lung adenocarcinoma cell growth and migration by interacting with ZSWIM1 and promoting its degradation.

Contribution

The novel finding is that TRIM21 suppresses ZSWIM1's oncogenic effects through ubiquitination in lung adenocarcinoma.

Findings

TRIM21 interacts with and co-localizes with ZSWIM1 in LUAD cells.

TRIM21 overexpression reduces ZSWIM1's promotion of cell proliferation and migration.

TRIM21 enhances ZSWIM1 ubiquitination, lowering its protein levels.

Abstract

肺腺癌（lung adenocarcinoma, LUAD）是一种致病率和死亡率都极高的癌症，尽管现代医学的治疗手段在不断进步，但患者的5年生存率仍不高，因此我们想通过探究LUAD发生发展的分子机制进而鉴定新的治疗靶标。我们前期的研究报道了ZSWIM1（zinc finger SWIM-type containing 1）是一个促进LUAD细胞增殖、迁移、侵袭的新蛋白。本研究将着重探究E3泛素连接酶TRIM21（tripartite-motif protein 21）对ZSWIM1在LUAD细胞中促增殖、迁移功能的影响。

利用蛋白免疫共沉淀技术（co-immunoprecipitation, Co-IP）和免疫荧光技术（immunofluorescence, IF）验证TRIM21和ZSWIM1之间的相互作用和共定位；利用MTT和Transwell实验检测TRIM21及TRIM21、ZSWIM1协同对LUAD增殖、迁移的影响；利用蛋白印迹实验（Western blot, WB）检测TRIM21和ZSWIM1对LUAD细胞上皮间充质转化（epithelial-mesenchymal transition, EMT）标志物表达的影响；利用Co-IP联合WB检测TRIM21对ZSWIM1泛素化的影响。

TRIM21与ZSWIM1存在相互作用和共定位。TRIM21的上调可以抑制LUAD细胞的增殖和迁移。过表达TRIM21能够降低ZSWIM1对LUAD细胞增殖、迁移和侵袭的促进作用，并逆转ZSWIM1对E-cadherin和Vimentin表达的影响。敲低TRIM21则可以增强ZSWIM1对LUAD细胞增殖和迁移的促进作用。机制方面，我们发现过表达TRIM21可明显增强ZSWIM1的泛素化水平，下调ZSWIM1的蛋白表达量。

TRIM21通过结合并促进ZSWIM1的泛素化，进而降低ZSWIM1的蛋白表达，这抑制了ZSWIM1对LUAD细胞增殖、迁移、侵袭表型的促进作用。

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