Li X, Hao XX, Zhu RQ, Zhou HW. Molecular mechanism of non-coding RNAs-mediated radiosensitivity regulation in colorectal cancer. World J Gastrointest Oncol 2025; 17(12): 113636 [DOI: 10.4251/wjgo.v17.i12.113636]
Corresponding Author of This Article
Xiao Li, MD, PhD, Department of General Medicine, The Fourth Medical Center of Chinese PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing 100048, China. nklx@foxmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Review
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/
World J Gastrointest Oncol. Dec 15, 2025; 17(12): 113636 Published online Dec 15, 2025. doi: 10.4251/wjgo.v17.i12.113636
Molecular mechanism of non-coding RNAs-mediated radiosensitivity regulation in colorectal cancer
Xiao Li, Xiu-Xia Hao, Rui-Qing Zhu, Hong-Wei Zhou
Xiao Li, Xiu-Xia Hao, Hong-Wei Zhou, Department of General Medicine, The Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, China
Rui-Qing Zhu, Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
Co-first authors: Xiao Li and Xiu-Xia Hao.
Co-corresponding authors: Xiao Li and Hong-Wei Zhou.
Author contributions: Li X and Hao XX contributed equally as co-first authors; Li X and Zhou HW designed the framework and content of this article, and made equal contributions as co-corresponding authors; Li X, Zhu RQ, and Hao XX completed the literature review and article writing; Li X summarized the tables; all authors did critical revision of this article and have approved the final draft submitted.
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: Xiao Li, MD, PhD, Department of General Medicine, The Fourth Medical Center of Chinese PLA General Hospital, No. 51 Fucheng Road, Haidian District, Beijing 100048, China. nklx@foxmail.com
Received: August 31, 2025 Revised: September 25, 2025 Accepted: October 28, 2025 Published online: December 15, 2025 Processing time: 103 Days and 15.1 Hours
Abstract
Colorectal cancer (CRC) remains a formidable global health challenge and is associated with dismal survival outcomes and high mortality among patients diagnosed at advanced stages. Despite advancements in early screening and therapeutic interventions, the outcomes of patients with advanced-stage CRC remain suboptimal, as these patients continue to exhibit a persistently low 5-year survival rate. Palliative radiotherapy (RT) is crucial for advanced CRC patients, but radioresistance remains a significant clinical challenge. This resistance is attributed to multiple mechanisms, such as genetic heterogeneity, dysregulated DNA damage repair and tumor microenvironment metabolic disorders. Recent studies have shown that noncoding RNAs (ncRNAs), mainly microRNAs, long ncRNAs (lncRNAs) and circular RNAs, play pivotal roles in regulating CRC radiosensitivity through diverse mechanisms, such as epithelial-mesenchymal transition, epigenetic reprogramming, posttranscriptional regulation and oncogenic signaling pathway activation. For example, microRNAs such as miR-141-3p and miR-630 enhance CRC radiosensitivity by targeting oncogenic pathways. In addition, lncRNAs, including the lncRNAs HOTAIR and LINC00630, influence the radiosensitivity of CRC through interactions with the DNA damage repair machinery and epigenetic modulators, respectively. In addition, circ_0124554 acts as a competitive endogenous RNA to regulate oncogenic signaling. ncRNAs also serve as potential biomarkers for predicting radiosensitivity and prognosis. This review synthesizes the current evidence on the ncRNA-mediated regulatory networks that influence CRC radiosensitivity, emphasizing their potential as therapeutic targets to overcome RT resistance and improve outcomes in advanced CRC. By bridging mechanistic insights with clinical applications, this work aims to guide future research and the implementation of precision RT strategies.
Core Tip: Colorectal cancer (CRC), a leading cause of cancer mortality, shows less than 10% 5-year survival in advanced stages and radiotherapy is crucial for advanced CRC patients. Noncoding RNAs (ncRNAs), including microRNAs, long ncRNAs and circular RNAs, significantly influence CRC radiosensitivity through diverse mechanisms like epithelial-mesenchymal transition, epigenetic reprogramming, post-transcriptional regulation and oncogenic signaling pathways activation. They show promise as biomarkers for predicting radiosensitivity and prognosis, and as therapeutic targets to overcome radioresistance. Targeting ncRNA-mediated networks offers promising strategies to overcome radioresistance and improve outcomes, bridging molecular mechanisms with precision radiotherapy for advanced CRC.
