Overexpression of BZW1 promotes invasion and metastasis of gastric cancer cells by regulating Wnt/β-catenin signaling and promoting epithelial-mesenchymal transition
10.12122/j.issn.1673-4254.2024.02.18
- VernacularTitle:BZW1高表达促进胃癌细胞的侵袭和转移:基于调控Wnt//β-catenin通路和促进上皮间质转化
- Author:
Wenjing ZHANG
1
;
Nuo ZHANG
;
Zi YANG
;
Xiaofeng ZHANG
;
Aofei SUN
;
Lian WANG
;
Xue SONG
;
Zhijun GENG
;
Jing LI
;
Jianguo HU
Author Information
1. 蚌埠医学院第一附属医院 检验科,安徽 蚌埠 233004
- Keywords:
gastric cancer;
basic leucine zipper and W2 domain-containing protein 1;
prognosis;
epithelial-mesenchymal transition;
Wnt/β-catenin
- From:
Journal of Southern Medical University
2024;44(2):354-362
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the expression level of basic leucine zipper and W2 domain-containing protein 1(BZW1)in gastric cancer,its impact on patient prognosis and the underlying mechanisms.Methods TIMER,UALCAN and Kaplan-Meier Plotter databases were used for analyzing BZW1 expression level gastric cancer tissues and its correlation with tumor grade and stage and the patients'prognosis.We further analyzed BZW1 expressions,disease progression,and postoperative 5-year survival in 102 patients undergoing radical surgery for gastric cancer at our hospital between January,2014 and December,2016.Gastric cancer MGC803 cells were examined for changes in migration,invasion,and epithelial-mesenchymal transition(EMT)following lentivirus-mediated BZW1 overexpression or knockdown.Results The protein and mRNA expressions of BZW1 in gastric cancer tissues were 3.30 and 6.54 times of those in adjacent tissues,respectively(P<0.01).BZW1 expression in gastric cancer tissues were positively correlated with peripheral blood CEA and CA199 levels(P<0.01).A high BZW1 expression was an independent risk factor for 5-year survival of gastric cancer patients after radical surgery(P<0.05,HR=2.070,95%CI:1.021-4.196).At the cut-off value of 3.61,BZW1 expression had a sensitivity of 75.56%and a specificity of 71.93%for predicting postoperative 5-year mortality(P<0.01).In MGC803 cells,BZW1 overexpression obviously promoted cell migration and invasion(P<0.05),enhanced cellular expressions of N-cadherin and vimentin(P<0.05)and inhibited the expression of E-cadherin(P<0.05).Enrichment analysis suggested the involvement of BZW1 in the Wnt/β-catenin signaling pathway.Western blotting confirmed that BZW1 overexpression promoted while BZW1 knockdown inhibited the expressions of Wnt3a,β-catenin and C-myc in MGC803 cells(P<0.05).Conclusion BZW1 is highly expressed in gastric cancer tissues to affect the patient prognosis possibly by activation the Wnt/β-catenin signaling pathway to promote EMT of gastric cancer cells.
