Xu YJ, Huo YC, Zhao QT, Liu JY, Tian YJ, Yang LL, Zhang Y. NOX4 promotes tumor progression through the MAPK-MEK1/2-ERK1/2 axis in colorectal cancer. World J Gastrointest Oncol 2024; 16(4): 1421-1436 [PMID: 38660653 DOI: 10.4251/wjgo.v16.i4.1421]
Corresponding Author of This Article
Yi Zhang, MD, PhD, Chief Physician, Full Professor, Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, Henan Province, China. yizhang@zzu.edu.cn
Research Domain of This Article
Oncology
Article-Type of This Article
Clinical and Translational Research
Open-Access Policy of This Article
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/
Apr 15, 2024 (publication date) through Feb 27, 2026
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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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Xu YJ, Huo YC, Zhao QT, Liu JY, Tian YJ, Yang LL, Zhang Y. NOX4 promotes tumor progression through the MAPK-MEK1/2-ERK1/2 axis in colorectal cancer. World J Gastrointest Oncol 2024; 16(4): 1421-1436 [PMID: 38660653 DOI: 10.4251/wjgo.v16.i4.1421]
Yu-Jie Xu, Ya-Chang Huo, Qi-Tai Zhao, Jin-Yan Liu, Yi-Jun Tian, Lei-Lei Yang, Yi Zhang, Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Yu-Jie Xu, Department of Oncology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou 450003, Henan Province, China
Co-first authors: Yu-Jie Xu and Ya-Chang Huo.
Author contributions: Xu YJ and Huo YC equally contributed to this work. Xu YJ, Huo YC, and Zhao QT analyzed the data; Xu YJ performed the experiments and drafted the manuscript; Huo YC and Zhao QT prepared the figures; Liu JY and Tian YJ performed hematoxylin-eosin and immunohistochemical staining experiments; Yang LL corrected the figures; Zhang Y designed, supervised and supported the study, and edited the manuscript; and all authors have read and approve the final the manuscript.
Supported byHenan Province Medical Science and Technology Research Provincial and Ministry Co-constructed Projects, No. SBGJ202101010; Major Public Welfare Projects in Henan Province, No. 201300310400; Joint Construction Project of Henan Medical Science and Technology Research Plan, No. LHGJ20220050; and Major Science and Technology Project of Henan Province, No. 221100310100.
Institutional review board statement: Approval of the research protocol by the Committee of First Affiliated Hospital of Zhengzhou University (No. 2022-KY-0828-003).
Clinical trial registration statement: This manuscript is not a Clinical Trial. The clinical part in the manuscript is a retrospective analysis. So we don’t have a clinical trial registration statement.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All public data can be downloaded from TCGA through online database UCSC Xena (xena.ucsc.edu) and GEO using the access number: GSE17536. Other data used in the study are available from the corresponding author upon reasonable request.
Corresponding author: Yi Zhang, MD, PhD, Chief Physician, Full Professor, Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, Henan Province, China. yizhang@zzu.edu.cn
Received: December 8, 2023 Peer-review started: December 8, 2023 First decision: December 21, 2023 Revised: January 4, 2024 Accepted: February 7, 2024 Article in press: February 7, 2024 Published online: April 15, 2024 Processing time: 124 Days and 12.9 Hours
ARTICLE HIGHLIGHTS
Research background
Colorectal cancer (CRC) is the leading cause of cancer-related death. Although conventional therapy has improved the prognosis of CRC, majority of patient do not well respond to these therapies. Therefore, identification of new targets is urgent for CRC.
Research motivation
Metabolic reprogramming is the major cause of therapy failure. In this study, we aim to explore the metabolic alteration in CRC tumor tissue and identify the key metabolic genes mediated this process.
Research objectives
We aim to explore the differently expressed metabolic genes between tumor and normal tissue as well as correlated with survival. In addition, we want to construct a prediction model based on this metabolic gene and identify key metabolic genes.
Research methods
We used bioinformatics analysis to identify differently expressed genes and survival related genes. Cox regression model was used to construct prediction model. Tumor biology experiments and in vivo mouse model were used to validate the role of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in mediating CRC progression.
Research results
We found that most of metabolic genes were dys-regulated between tumor and normal tissue. The NOX4 was the key metabolic gene that promoted proliferation, migration invasion and stemness of tumor cell through mitogen-activated protein kinase signaling pathway. In vivo mouse models, over-expression of NOX4 increased tumor growth and metastasis.
Research conclusions
NOX4 is a key metabolic gene that promote CRC progression.
Research perspectives
Combined therapies with targeting NOX4 may be a promising strategy for CRC treatment.
