ZNF710 regulates the proliferation, migration, apoptosis, and cell cycle progression of gastric cancer cells through the Wnt/β-catenin pathway

Runkai Zhou; Jingyi Zhou; Jinfeng Cai; Jiazhe Wen; Fazhi Wang; Di Ma; Qingshan Luo; Abudushalamu Yalikun; Jinlu Han; Xuefeng Zhou; Yang Yu; Qi Li; Yugang Wen

doi:10.62347/HCCY8796

ZNF710 regulates the proliferation, migration, apoptosis, and cell cycle progression of gastric cancer cells through the Wnt/β-catenin pathway

Am J Cancer Res. 2025 Dec 25;15(12):5266-5280. doi: 10.62347/HCCY8796. eCollection 2025.

Authors

Runkai Zhou¹, Jingyi Zhou², Jinfeng Cai¹, Jiazhe Wen³, Fazhi Wang¹, Di Ma², Qingshan Luo¹, Abudushalamu Yalikun¹, Jinlu Han⁴, Xuefeng Zhou⁵, Yang Yu¹, Qi Li², Yugang Wen¹

Affiliations

¹ Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200080, China.
² Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200080, China.
³ School of Basic Medical Sciences, Fudan University Shanghai 200032, China.
⁴ Department of Gastroenterology, Shanghai Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 200336, China.
⁵ Department of Oncology, The Dongtai Hospital of Nantong University Yancheng 224200, Jiangsu China.

Abstract

Objective: This study aimed to investigate the mechanism underlying the role of Zinc finger protein 710 (ZNF710) in gastric cancer (GC).

Methods: The level of ZNF710 expression in GC and its prognosis were examined based on the public databases and clinical samples. Cell models of lentivirus-mediated overexpression (oeZNF710) and knockdown (shZNF710) of ZNF710 were developed on the AGS and HGC-27 GC cell lines. The biological behaviors of these cells were analysed systematically, comprising proliferation (as measured by CCK-8 assay and plate cloning experiment), apoptosis (measured by flow cytometry), and migration (measured by Transwell assay). To confirm the expression of the main proteins of the Wnt/β-catenin system, western blotting analysis was conducted. Besides, functional rescue experiments of Wnt signaling agonist SKL2001 and Wnt signaling inhibitor XAV939 were performed. The in vivo activity of ZNF710 was tested in a nude mouse subcutaneous xenograft model.

Results: The expression of ZNF710 was significantly increased in GC tissues and cell lines compared to standard controls, whereas high levels of ZNF710 were associated with a poor prognosis in GC patients. ZNF710 knockdown of HGC-27 cells significantly reduced cell proliferation, migration, and invasion and increased apoptosis. On the contrary, overexpression of ZNF710 in AGS cells produced the reverse effects. Mechanistically, ZNF710 overexpression increased the expression of Wnt/β-catenin pathway-related regulatory proteins, and ZNF710 knockdown reduced their expression.

Conclusion: ZNF710 is highly expressed in GC and promotes GC cell proliferation, migration, and invasion while inhibiting apoptosis by activating the Wnt/β-catenin pathway, suggesting it may serve as a potential therapeutic target for GC.

Keywords: Wnt/β-catenin; Zinc finger protein; cell cycle; gastric cancer.