# 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.

## Key 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。