Mao HQ, Yu FC, Hu DQ, Zhang LJ. Myc-associated zinc finger protein drives colorectal cancer metastasis through activating ubiquitin like with ring finger protein one. World J Gastrointest Oncol 2025; 17(11): 109481 [DOI: 10.4251/wjgo.v17.i11.109481]
Corresponding Author of This Article
Hui-Qin Mao, Department of Ultrasonography, The Third People’s Hospital of Yuhang District, No. 8 Yangshanwan Road, Pingyao Town, Yuhang District, Hangzhou 311115, Zhejiang Province, China. 13968523585@163.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Nov 15, 2025 (publication date) through Nov 13, 2025
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Journal Information of This Article
Publication Name
World Journal of Gastrointestinal Oncology
ISSN
1948-5204
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Mao HQ, Yu FC, Hu DQ, Zhang LJ. Myc-associated zinc finger protein drives colorectal cancer metastasis through activating ubiquitin like with ring finger protein one. World J Gastrointest Oncol 2025; 17(11): 109481 [DOI: 10.4251/wjgo.v17.i11.109481]
Hui-Qin Mao, Fang-Cao Yu, Li-Jing Zhang, Department of Ultrasonography, The Third People’s Hospital of Yuhang District, Hangzhou 311115, Zhejiang Province, China
Dan-Qiong Hu, Department of Gastroenterology, The Third People’s Hospital of Yuhang District, Hangzhou 311115, Zhejiang Province, China
Author contributions: Mao HQ contributed to conceptualization, methodology, and writing, review and editing; Yu FC and Hu DQ contributed to investigation and experiment; Zhang LJ contributed to data curation. All authors read and approved the final manuscript.
Supported by Hangzhou Medical and Health Science and Technology Plan, No. B20210014.
Institutional animal care and use committee statement: The protocol for animal experiment was approved by the Ethics Committee of Zhejiang Baiyue Biotech Co., Ltd for experimental animals welfare, No. ZJBYLA-IACUC-20240830.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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 datasets used or analyzed during the current study are available from the corresponding author on reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hui-Qin Mao, Department of Ultrasonography, The Third People’s Hospital of Yuhang District, No. 8 Yangshanwan Road, Pingyao Town, Yuhang District, Hangzhou 311115, Zhejiang Province, China. 13968523585@163.com
Received: June 24, 2025 Revised: August 12, 2025 Accepted: October 20, 2025 Published online: November 15, 2025 Processing time: 142 Days and 17.3 Hours
Abstract
BACKGROUND
Colorectal cancer (CRC) is one of the most common causes of cancer mortality worldwide. The transcription factor Myc-associated zinc finger protein (MAZ) has been implicated in cancer progression. However, its precise function and mechanisms in CRC remain unclear.
AIM
To investigate the role and mechanism of the MAZ/ubiquitin-like with PHD and RING finger domains 1 (UHRF1)/esophageal cancer-related gene 4 (ECRG4) axis in CRC metastasis.
METHODS
Western blot, quantitative reverse transcription polymerase chain reaction (PCR) and transwell were performed to evaluate the impact of MAZ knockdown on CRC cell migration and invasion. A xenograft tumor metastasis model was established by injecting MAZ-deficient CRC cells into nude mice to assess in vivo metastatic potential. Dual-luciferase reporter assay was performed to determine the role of MAZ and its downstream target, UHRF1. Chromatin immunoprecipitation-quantitative PCR and methylation-specific PCR were used to analyze whether UHRF1 regulated ECRG4 through DNA methylation.
RESULTS
MAZ was highly upregulated in CRC cells and promoted CRC migration, invasion, epithelial-mesenchymal transition (EMT) and metastasis. Mechanistically, MAZ transcriptionally activated UHRF1, which in turn led to DNA methylation of ECRG4. Knockdown of MAZ suppressed CRC migration and invasion was reversed by overexpression of UHRF1. Loss of UHRF1 upregulated ECRG4, inhibited EMT, and reduced cell migration and invasion. However, simultaneous knockdown of ECRG4 partially reversed these effects.
CONCLUSION
MAZ promotes CRC cell migration, invasion, and EMT by transcriptionally activating UHRF1, which downregulates ECRG4 through DNA methylation.
Core Tip: This study elucidated the oncogenic role of Myc-associated zinc finger protein (MAZ) in colorectal cancer (CRC), demonstrating its ability to promote cancer cell migration, invasion, and epithelial-mesenchymal transition by modulating the ubiquitin-like with PHD and RING finger domains 1-esophageal cancer-related gene 4 signaling pathway. MAZ was up-regulated in CRC cell species, and inhibition of its expression significantly inhibited cell invasion, invasion, epithelial-mesenchymal transition and tumor metastasis. Dual-luciferase reporter assay, chromatin immunoprecipitation quantitative polymerase chain reaction and methylation-specific polymerase chain reaction further validated the interaction of the MAZ-ubiquitin-like with PHD and RING finger domains 1-esophageal cancer-related gene 4 axis, providing convincing evidence for MAZ as a potential therapeutic target for CRC.
