Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Gastrointest Oncol. Sep 15, 2026; 18(9): 120170
Published online Sep 15, 2026. doi: 10.4251/wjgo.120170
Published online Sep 15, 2026. doi: 10.4251/wjgo.120170
IQGAP1 promotes tumor progression by stabilizing MCM3/Nrf2 in cholangiocarcinoma
Zhi-Yuan Ren, Hong-Yan Zhang, Chen-Xi Xie, Geng-Ping Zhou, Peng-Yu Chen, Hao Yuan, Kai Zhang, Yang Xu, Yang-Yang Wang, Tai-Yang Chen, Hepatobiliary Center, Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
Qing-Shan Li, National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Hai-Bo Yu, Department of Hepatobiliary and Pancreatic Surgery, People’s Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China
Co-first authors: Zhi-Yuan Ren and Hong-Yan Zhang.
Co-corresponding authors: Qing-Shan Li and Hai-Bo Yu.
Author contributions: Ren ZY and Zhang HY contribute equally to this study as co-first authors; Li QS and Yu HB contribute equally to this study as co-corresponding authors; Yu HB and Li QS completed conception and design; Ren ZY, Xie CX and Zhou GP completed development of methodology; Zhang HY, Chen PY, Yuan H and Zhang K completed collection and acquisition of data; Xu Y, Wang YY and Chen TY completed analysis of data; Yu HB, Li QS, Ren ZY and Xie CX completed writing, review, and/or revision of the manuscript; and all the authors have read and approved the final manuscript.
Supported by Henan Young and Middle-Aged Health Science and Technology Innovation Leading Talents Training Project, No. YXKC2022002.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Animal Ethical and Welfare Committee of Guangzhou Yongnuo Medical Experimental Animal Center (Approval No. IACUC-AEWC-F250801002).
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The original contributions presented in the study are included in the article and Supplementary material, and further inquiries can be directed to the corresponding authors.
Corresponding author: Hai-Bo Yu, PhD, Professor, Department of Hepatobiliary and Pancreatic Surgery, People’s Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou 450003, Henan Province, China. yhb2101661@zzu.edu.cn
Received: February 24, 2026
Revised: April 6, 2026
Accepted: May 7, 2026
Published online: September 15, 2026
Processing time: 189 Days and 22.8 Hours
Revised: April 6, 2026
Accepted: May 7, 2026
Published online: September 15, 2026
Processing time: 189 Days and 22.8 Hours
Core Tip
Core Tip: This study reveals for the first time that IQGAP1 drives cholangiocarcinoma progression by recruiting ubiquitin-specific peptidase 28 to stabilize MCM3 protein, inhibiting its ubiquitination. This stabilization activates the Nrf2 pathway, alleviating oxidative stress and suppressing apoptosis, thereby promoting tumor cell survival and growth. Inhibition of MCM3 reverses these effects. The findings identify IQGAP1 as a key regulator of the MCM3/Nrf2 axis and a promising therapeutic target.