ZNF384-mediated FZD3/Wnt signaling in the progression and chemoresistance of esophageal squamous cell carcinoma
10.13315/j.cnki.cjcep.2025.10.005
- VernacularTitle:ZNF384介导的FZD3/Wnt信号通路在食管鳞状细胞癌进展与化疗耐药中的研究
- Author:
Xiaoxu LI
1
;
Juntao LU
;
Zhaoyang YAN
;
Tongxin XU
;
Yan ZHAO
;
Wei GUO
Author Information
1. 河北医科大学第四医院放疗科,石家庄 050011
- Publication Type:Journal Article
- Keywords:
esophageal neoplasms;
squamous cell carcinoma;
ZNF384;
FZD3;
Wnt signaling pathway
- From:
Chinese Journal of Clinical and Experimental Pathology
2025;41(10):1291-1300
- CountryChina
- Language:Chinese
-
Abstract:
Purpose This study aimed to investigate the expression,function,and molecular mechanisms of ZNF384 in esophageal squamous cell carcinoma(ESCC),as well as its role in tumor progression and chemoresistance.Methods The expression of ZNF384 in ESCC cell lines and tissues was assessed using RT-qPCR.Correlations with TNM stage,invasion depth,lymph node metastasis,and prognosis were evaluated.In vitro assays were performed to examine the effects of ZNF384 on ESCC cell proliferation,migration,invasion,and chemosensitivity.Dual-luciferase reporter assays were conducted to determine the interaction between ZNF384 and FZD3,and to assess the activation of the Wnt signaling pathway.Results ZNF384 expression was significantly upregulated in ESCC cell lines and tissues(P＜0.01).Elevated ZNF384 expression was associated with advanced TNM stage,greater invasion depth,lymph node metastasis,and poor prognosis(P＜0.05).Functional assays demonstrated that ZNF384 overexpression promo-ted ESCC cell proliferation,migration,and invasion(all P＜0.01),whereas ZNF384 knockdown inhibited these processes and enhanced chemosensitivity to cisplatin(all P＜0.01).Mechanistic studies showed that ZNF384 directly bound to the FZD3 promoter,upregulated FZD3 expression,and activated the Wnt signaling pathway(P＜0.05).Overexpression of FZD3 partially reversed the inhibitory effects of ZNF384 knockdown on cell malignancy and chemore-sistance(P＜0.05).Conclusion ZNF384 promotes ESCC progression and reduces chemosensitivity through activa-tion of the FZD3/Wnt signaling pathway,suggesting its potential as a therapeutic target in ESCC.
