Role of CHMP4C in gastric cancer development through regulating necroptosis and its action mechanism
10.3969/j.issn.1009-9905.2025.02.006
- VernacularTitle:CHMP4C调控坏死性凋亡促进胃癌的作用及机制研究
- Author:
Qi-ning GUO
1
;
Ya-ping LI
;
Li PEI
;
Long-chen YU
;
Zheng-dong LUO
;
Rui ZHAO
;
Zhong-fang NIU
;
Xin ZHANG
Author Information
1. 山东大学齐鲁医院 检验科(山东 济南 250012)
- Publication Type:Journal Article
- Keywords:
Gastric neoplasms;
Chromatin Modifying Protein 4C;
Necroptosis;
Target
- From:
Chinese Journal of Current Advances in General Surgery
2025;28(2):125-133
- CountryChina
- Language:Chinese
-
Abstract:
Objective:Exploring the role and mechanism of CHMP4C in regulating necroptosis during gastric can-cer development and progression.Method:The expression of CHMP4C in pan-cancer was analyzed by bioinformatics methods,and the expression of CHMP4C was detected in human normal gastric epithelial cells and GC cell lines by RT-qPCR and Western blot.Overexpression or knockdown of CHMP4C was performed in GC cell lines,and the effects of CHMP4C on the growth and proliferation of GC cells were detected using CCK-8 and clone formation assays.The CCK-8 experiment and Hoechst/PI double staining experiment were used to detect the changes in GC cell mortality and PI positive cell ratio after treatment with the necroptsis inducer TSZ or inhibitor necrostatin-1(Nec-1).Western blot assay was used to detect the protein and phosphorylation levels of RIPK1,RIPK3,and MLKL in GC cells.Result:CHMP4C was upregulated in GC tissues and cells.The CCK-8 and clone formation experiments showed that overex-pression of CHMP4C significantly improved the proliferation ability and colony formation efficiency of GC cells,while knockdown of CHMP4C significantly weakened GC cells.Moreover,the results of CCK-8 and Hoechst 33342/PI double staining experiments showed that upregulated CHMP4C could inhibit TSZ induced GC cell death;Nec-1 can reverse the decrease in GC cell viability caused by CHMP4C knockdown.Western blot experiment showed that the levels of p-RIPK1,p-RIPK3,and p-MLKL were significantly decreased in overexpressing cells,while they were increased in knockdown cells.After treatment with Nec-1,the expression levels of these three proteins decreased in knockdown cells.Conclusion:CHMP4C may promote GC progression by negatively regulating necroptosis through inhibiting the phosphorylation of the RIPK1/RIPK3/MLKL signaling pathway,suggesting that it is expected to be a potential target for GC therapy.
