High expression of CDKN3 promotes migration and invasion of gastric cancer cells by regulating the p53/NF-κB signaling pathway and inhibiting cell apoptosis.
10.12122/j.issn.1673-4254.2025.04.21
- Author:
Yi ZHANG
1
;
Yu SHEN
1
;
Zhiqiang WAN
1
;
Song TAO
1
;
Yakui LIU
1
;
Shuanhu WANG
1
Author Information
1. Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui 233030, China.
- Publication Type:Journal Article
- Keywords:
CDKN3;
apoptosis;
gastric cancer;
p53/NF-κB;
prognosis;
proliferation
- MeSH:
Humans;
Stomach Neoplasms/pathology*;
Apoptosis;
Signal Transduction;
Tumor Suppressor Protein p53/metabolism*;
Cell Movement;
Cell Line, Tumor;
NF-kappa B/metabolism*;
Prognosis;
Cyclin-Dependent Kinase Inhibitor Proteins/metabolism*;
Cell Proliferation;
Neoplasm Invasiveness;
Male;
Female;
Dual-Specificity Phosphatases
- From:
Journal of Southern Medical University
2025;45(4):853-861
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the expression of CDKN3 in gastric cancer and its impact on prognosis of gastric cancer patients.
METHODS:We analyzed CDKN3 expression in clinical specimens from 114 gastric cancer patients and assessed its association with 5-year postoperative survival of the patients. GO and KEGG enrichment analyses were used to predict the biological function and possible mechanism of CDKN3. The effects of lentivirus-mediated CDKN3 knockdown on biological behaviors of gastric cancer cells were evaluated using Transwell assay, CCK-8 assay, TUNEL staining, flow cytometry, and Western blotting.
RESULTS:CDKN3 expression was significantly higher in gastric cancer tissues than in the adjacent tissues with significant correlations with CEA level, CA19-9 level, and T and N staging (P<0.05). High CDKN3 expression was an independent risk factor affecting 5-year postoperative survival of the patients and predictive for long-term prognosis (P<0.01). Enrichment analyses suggested a probable association of CDKN3 with apoptosis. In MGC-803 cells, CDKN3 knockdown significantly lowered migration and invasion capacities of the cells, while CDKN3 overexpression produced the opposite effects. TUNEL staining revealed a significantly lower level of cell apoptosis in gastric cancer tissues than in adjacent tissues (P<0.01). CDKN3 knockdown obviously inhibited proliferation and increased apoptosis of MGC-803 cells. CDKN3 overexpression down-regulated the expressions of p53, p21 and Bax and up-regulated the expressions of p-p65 and Bcl-2.
CONCLUSIONS:CDKN3 is highly expressed in gastric cancer tissues and affects patient prognosis. CDKN3 overexpression promotes proliferation, invasion and migration and suppressed apoptosis of gastric cancer cells possibly through the p53/NF-κB signaling pathway.
