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17(12): 113636  \nDOI: 10.4251/wjgo.v17.i12.113636 ISSN 1948-5204 (online)  \nREVIEW  \nMolecular mechanism of non-coding RNAs-mediated radiosensitivity regulation in colorectal cancer  \nXiao Li, Xiu-Xia Hao, Rui-Qing Zhu, Hong-Wei Zhou  \nSpecialty type: Gastroenterology and hepatology  \nProvenance and peer review:  \nInvited article; Externally peer reviewed.  \nPeer-review model: Single blind  \nPeer-review report’s classification Scientific Quality: Grade B, Grade B  \nNovelty: Grade B, Grade C  \nCreativity or Innovation: Grade C, Grade C  \nScientific Significance: Grade B, Grade C  \nP-Reviewer: Suda T, MD, PhD, Professor, Japan  \nReceived: August 31, 2025  \nRevised: September 25, 2025  \nAccepted: October 28, 2025  \nPublished online: December 15, 2025  \nProcessing time: 103 Days and 15 Hours  \nXiao Li, Xiu-Xia Hao, Hong-Wei Zhou, Department of General Medicine, The Fourth Medical Center of Chinese PLA General Hospital, Beijing 100048, China  \nRui-Qing Zhu, Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China  \nCo-first authors: Xiao Li and Xiu-Xia Hao.  \nCo-corresponding authors: Xiao Li and Hong-Wei Zhou.  \nCorresponding 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.](China. nklx@foxmail.com)[ nklx@foxmail.com](China. nklx@foxmail.com)  \nAbstract  \nColorectal 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  \n WJGO  [https://www.wjgnet.com](https://www.wjgnet.com) 1 December 15, 2025  Volume 17  Issue 12   \nLi X et al. ncRNA-mediated radiosensitivity in CRC  \nto guide future research and the implementation of precision RT strategies.  \nKey Words: Radiosensitivity; Noncoding RNAs; Colorectal cancer; Radiotherapy; Radioresistance  \n©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.  \nCore Tip: Colorectal cancer (CRC), a leading ","cbCaivajnorGjkpR","https://ap.wps.com/l/cbCaivajnorGjkpR","pdf",535712,13,"English","# Introduction\n# Molecular mechanisms and ncRNA networks","[{\"question\":\"Why is radiosensitivity important in advanced colorectal cancer?\",\"answer\":\"Palliative radiotherapy is used to control tumors and reduce complications in advanced CRC, but treatment effectiveness is limited by radioresistance, which worsens clinical outcomes.\"},{\"question\":\"What mechanisms contribute to radioresistance in colorectal cancer?\",\"answer\":\"Radioresistance is linked to genetic heterogeneity, dysregulated DNA damage repair, and tumor microenvironment metabolic disorders.\"},{\"question\":\"How do non-coding RNAs influence colorectal cancer radiosensitivity?\",\"answer\":\"Noncoding RNAs (microRNAs, long ncRNAs, and circular RNAs) regulate radiosensitivity through mechanisms such as EMT, epigenetic reprogramming, post-transcriptional regulation, and activation of oncogenic signaling pathways.\"}]","Molecular mechanism of non-coding RNAs-mediated radiosensitivity regulation in colorectal cancer | PDF",1790566642,33]