2. Academic Validation
  3. Helicobacter pylori activates DOPEY1 to promote p53 degradation through the USP7/TRIP12 axis in gastric tumorigenesis

Helicobacter pylori activates DOPEY1 to promote p53 degradation through the USP7/TRIP12 axis in gastric tumorigenesis

  • Oncogene. 2025 Feb 12. doi: 10.1038/s41388-025-03303-5.
Yan-An Zhou # 1,  Nian-Shuang Li # 1,  Yu-Chen Zhu 1,  Ze-Kun He 2,  Yaobin Ouyang 1,  Li-Xiang Ling 1,  Xi-Dong Wu 3,  Hui-Qiao Zhou 1,  Huan Wang 1,  Xin-Bo Xu 1,  Xiao Fei 1,  Cong He 1,  Yu-Juan Dong 4,  Jianping Liu 1,  Nong-Hua Lu 1,  Yin Zhu 5,  Yi Hu 6 7
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
  • 2 Department of Gastroenterology, Yichun People's Hospital, Yichun, 336000, Jiangxi, China.
  • 3 Department of Drug Safety Evaluation Center, Nanchang Key Laboratory for Quality Evaluation of Medical Devices, Jiangxi Medical Device Testing Center, Nanchang, 330029, Jiangxi, China.
  • 4 Department of Surgery at the Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong, China.
  • 5 Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China. ndyfy01977@ncu.edu.cn.
  • 6 Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China. ndyfy06202@ncu.edu.cn.
  • 7 Department of Surgery at the Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong, China. ndyfy06202@ncu.edu.cn.
  • # Contributed equally.
PMID: 39939725 DOI: 10.1038/s41388-025-03303-5
Abstract

DOP1 leucine zipper-like protein A (DOPEY1), a member of the DOPEY family, is mainly localized in the Golgi apparatus, endosomes, and cytoplasmic compartments within cells. The involvement of DOPEY1 in H. pylori infection-induced carcinogenesis has remained unresolved. Here, we report that DOPEY1 is upregulated in GC tissues compared to adjacent normal tissues, correlating with poor prognosis. Mechanistically, H. pylori Infection increases DOPEY1 expression and promotes p53 degradation through a CagA-dependent pathway. Using the String database and liquid chromatography-mass spectrometry, we identified DOPEY1-interacting proteins, confirming through co-immunoprecipitation that DOPEY1 interacts with USP7 and TRIP12. H. pylori Infection enhances the expression of DOPEY1, USP7, and TRIP12, leading to p53 degradation, which is reversed by DOPEY1 silencing. Moreover, USP7 overexpression rescues p53 degradation in DOPEY1-silenced cells. Functionally, DOPEY1 knockdown reduces GC cell proliferation and suppresses tumor growth in mouse models. Immunohistochemistry analysis further reveals a link between DOPEY1, USP7, and TRIP12 expression, H. pylori Infection, and GC progression. These findings demonstrate that H. pylori-induced upregulation of DOPEY1 drives p53 degradation via the USP7/TRIP12 axis, contributing to gastric tumorigenesis, and highlight DOPEY1 as a potential therapeutic target for H. pylori-associated GC.

Figures
Products