Mutations and functional mechanisms of deubiquitinating enzyme OTU domain-containing protein 3 in colorectal cancer
10.7644/j.issn.1674-9960.2025.05.001
- VernacularTitle:去泛素化酶含OTU结构域蛋白3在结直肠癌中的突变及功能机制研究
- Author:
Jinhao ZHANG
1
;
Yonghui ZHANG
;
Hongchang LI
;
Lingqiang ZHANG
Author Information
1. 青岛大学基础医学院,山东青岛 266071
- Keywords:
colorectal cancer;
OTU domain-containing protein 3;
phosphatase and tensin homolog deleted on chromosome 10;
tumor associated-mutation;
ubiquitination
- From:
Military Medical Sciences
2025;49(5):321-329
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate mutations in OTU domain-containing protein 3(OTUD3)and their functional mechanisms in the initiation and progression of colorectal cancer(CRC).Methods Gene expression profiling interactive analysis(GEPIA2)and the human protein atlas database(THPA)were used to analyze gene transcription and protein expressions.Samples from 32 patients with CRC were collected to identify OTUD3 mutants.Based on the information about mutation sitesof OTUD3 in an existing database,a plasmid vector containing the OTUD3 gene mutant was constructed.Plasmid vectors containing the phosphatase and tensin homolog deleted on chromosome 10(PTEN)and the OTUD3 gene mutant were co-transfected into HCT116 cells.Western blotting,half-life,immunoprecipitation,ubiquitination,and hybrid algorithm molecular docking(H-DOCK)assays were employed to find out whether and why the OTUD3 mutants affected PTEN protein levels.Functional alterations in CRC cells after OTUD3 mutation were verified by CCK-8 cell proliferation,transwell cell invasion,scratch,and clonal formation assays.Results OTUD3 mutations were highly frequent in CRC.OTUD3 mutants R178W and N321S resulted in the loss of function of the stable PTEN protein,leading to enhanced proliferation,invasion,migration,and survival of CRC.Conclusion In CRC,OTUD3 mutation reduces the ability to stabilize PTEN and promotes the occurrence and development of CRC.
