TRIM21 Inhibits the Proliferation and Migration of Lung Adenocarcinoma Cells by Interacting with ZSWIM1
10.3779/j.issn.1009-3419.2024.101.13
- VernacularTitle:TRIM21通过与ZSWIM1相互作用调节肺腺癌细胞的增殖和迁移
- Author:
CHEN LUXUAN
1
,
2
;
LIAN QIONGHUA
;
ZHANG GUI
;
WU JIAYAO
;
ZENG GUANDI
;
GAO XUEJUAN
Author Information
1. 510632 广州,暨南大学肿瘤分子生物学教育部重点实验室,生物活性药物分子与成药性优化全国重点实验室,暨南大学生命与健康工程研究院
2. 510317 广州,暨南大学附属广东省第二人民医院,传统医学与运动伤害康复研究所
- Keywords:
Lung neoplasms;
TRIM21;
ZSWIM1;
Proliferation;
Migration
- From:
Chinese Journal of Lung Cancer
2024;27(5):337-344
- CountryChina
- Language:Chinese
-
Abstract:
Background and objective Lung adenocarcinoma(LUAD)is a highly morbid and fatal cancer.De-spite advancements in modern medical treatment,the 5-year survival rate of patients remains suboptimal.Our previous study revealed that zinc finger SWIM-type containing 1(ZSWIM1),a novel protein,promotes the proliferation,migration,and inva-sion of LUAD cells.The aim of this study is to investigate the impact ofE3 ubiquitin ligase tripartite motif protein 21(TRIM21)on ZSWIM1-mediated cell proliferation and migration.Methods The interaction and co-localization between TRIM21 and ZSWIM1 were verified using co-immunoprecipitation(Co-IP)and immunofluorescence(IF).The effects of TRIM21 and ZSWIM1 on the proliferation and migration of LUAD cells were assessed through MTT and Transwell assays,respectively.Western blot(WB)analysis was conducted to evaluate the impact of TRIM21 and ZSWIM1 on the expression of epithelial-mesenchymal transition(EMT)markers in LUAD cells.The influence of TRIM21 on the ubiquitination of ZSWIM1 was exam-ined using Co-IP combined with WB.Results TRIM21 was found to interact and co-localize with ZSWIM1.Overexpression of TRIM21 inhibited the proliferation and migration of LUAD cells.Overexpression of TRIM21 reduced the promoting effect of ZSWIM1 on the proliferation,migration,and invasion of lung adenocarcinoma cells,and reversed the impact of ZSWIM1 on the expression of E-cadherin and Vimentin.Conversely,knockdown of TRIM21 further enhanced the promoting effect of ZSWIM1 on the proliferation and migration of LUAD cells.Mechanistically,we observed that overexpression of TRIM21 significantly en-hanced the ubiquitination level of ZSWIM1,leading to a decrease in ZSWIM1 protein expression.Conclusion TRIM21 binds to and promotes the ubiquitination of ZSWIM1,resulting in reduced protein expression of ZSWIM1,which leads to the inhibition of ZSWIM1-mediated promotion of proliferation,migration,and invasion in LUAD cells.
