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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Dec 15, 2025; 17(12): 112753
Published online Dec 15, 2025. doi: 10.4251/wjgo.v17.i12.112753
Published online Dec 15, 2025. doi: 10.4251/wjgo.v17.i12.112753
Interlaced roles of mitochondrial DNA in colorectal cancer: Liquid-biopsy biomarkers, nuclear mtDNA-driven genomic instability, and mito-encoded micro peptide signaling
Thai-Hau Koo, Andee Dzulkarnaen Zakaria, Department of Surgery, Hospital Pakar Universiti Sains Malaysia, School of Medical Sciences, Kubang Kerian 16150, Kelantan, Malaysia
Xue-Bin Leong, Yi-Lin Lee, Universiti Sains Malaysia, School of Medical Sciences, Health Campus, Kubang Kerian 16150, Kelantan, Malaysia
Firdaus Hayati, Department of Surgery, Faculty of Medicine and Health Sciences, University Malaysia Sabah, Kota Kinabalu 88400, Sabah, Malaysia
Co-first authors: Thai-Hau Koo and Xue-Bin Leong.
Author contributions: Koo TH and Leong XB contributed equally as co-first authors. Koo TH, Hayati F, and Zakaria AD designed the overall concept and outline of the manuscript; Leong XB and Lee YL contributed to the discussion and design of the manuscript; Koo TH, Leong XB, Lee YL, and Zakaria AD contributed to the writing and editing of the manuscript, illustrations, and review of literature. All authors have read and approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Andee Dzulkarnaen Zakaria, Department of Surgery, Hospital Pakar Universiti Sains Malaysia, School of Medical Sciences, Jalan Raja Perempuan Zainab 2, Kubang Kerian 16150, Kelantan, Malaysia. andee@usm.my
Received: August 5, 2025
Revised: September 28, 2025
Accepted: November 12, 2025
Published online: December 15, 2025
Processing time: 128 Days and 17.2 Hours
Revised: September 28, 2025
Accepted: November 12, 2025
Published online: December 15, 2025
Processing time: 128 Days and 17.2 Hours
Core Tip
Core Tip: This minireviews highlights the emerging roles of mitochondrial DNA (mtDNA) in colorectal cancer beyond its role in energy metabolism. Three interrelated domains are focused on in this paper: (1) Cell-free mtDNA as a liquid biopsy biomarker of exceptional sensitivity; (2) Nuclear mtDNA fragments as a component of genomic instability; and (3) Mitochondria-derived peptides, such as humanin and mitochondrial open reading frame of the 12S rRNA type-c, as regulators of tumour behaviour. These insights reveal novel diagnostic and therapeutic potential by targeting mitochondrial-nuclear cross-talk in colorectal cancer.