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      Regulatory role of non-coding RNAs in 5-Fluorouracil resistance in gastrointestinal cancers

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          Abstract

          Gastrointestinal (GI) cancers are becoming a growing cause of morbidity and mortality globally, posing a significant risk to human life and health. The main treatment for this kind of cancer is chemotherapy based on 5-fluorouracil (5-FU). However, the issue of 5-FU resistance is becoming increasingly prominent, which greatly limits its effectiveness in clinical treatment. Recently, numerous studies have disclosed that some non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), exert remarkable physiological functions within cells. In addition, these ncRNAs can also serve as important information communication molecules in the tumor microenvironment and regulate tumor chemotherapy resistance. In particular, they have been shown to play multiple roles in regulating 5-FU resistance in GI cancers. Herein, we summarize the targets, pathways, and mechanisms involved in regulating 5-FU resistance by ncRNAs and briefly discuss the application potential of ncRNAs as biomarkers or therapeutic targets for 5-FU resistance in GI cancers, aiming to offer a reference to tackle issues related to 5-FU resistance.

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          Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation

          Jacob O'Brien, Heyam Hayder, Yara Zayed … (2018)
          MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in regulating gene expression. The majority of miRNAs are transcribed from DNA sequences into primary miRNAs and processed into precursor miRNAs, and finally mature miRNAs. In most cases, miRNAs interact with the 3′ untranslated region (3′ UTR) of target mRNAs to induce mRNA degradation and translational repression. However, interaction of miRNAs with other regions, including the 5′ UTR, coding sequence, and gene promoters, have also been reported. Under certain conditions, miRNAs can also activate translation or regulate transcription. The interaction of miRNAs with their target genes is dynamic and dependent on many factors, such as subcellular location of miRNAs, the abundancy of miRNAs and target mRNAs, and the affinity of miRNA-mRNA interactions. miRNAs can be secreted into extracellular fluids and transported to target cells via vesicles, such as exosomes, or by binding to proteins, including Argonautes. Extracellular miRNAs function as chemical messengers to mediate cell-cell communication. In this review, we provide an update on canonical and non-canonical miRNA biogenesis pathways and various mechanisms underlying miRNA-mediated gene regulations. We also summarize the current knowledge of the dynamics of miRNA action and of the secretion, transfer, and uptake of extracellular miRNAs.
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            Cancer and Radiation Therapy: Current Advances and Future Directions

            Rajamanickam Baskar, Kuo Lee, Richard Yeo … (2012)
            In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. However with its increasing incidence, the clinical management of cancer continues to be a challenge for the 21st century. Treatment modalities comprise of radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Radiation therapy remains an important component of cancer treatment with approximately 50% of all cancer patients receiving radiation therapy during their course of illness; it contributes towards 40% of curative treatment for cancer. The main goal of radiation therapy is to deprive cancer cells of their multiplication (cell division) potential. Celebrating a century of advances since Marie Curie won her second Nobel Prize for her research into radium, 2011 has been designated the Year of Radiation therapy in the UK. Over the last 100 years, ongoing advances in the techniques of radiation treatment and progress made in understanding the biology of cancer cell responses to radiation will endeavor to increase the survival and reduce treatment side effects for cancer patients. In this review, principles, application and advances in radiation therapy with their biological end points are discussed.
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              5-fluorouracil: mechanisms of action and clinical strategies.

              Daniel Longley, D. Paul Harkin, Patrick Johnston (2003)
              5-fluorouracil (5-FU) is widely used in the treatment of cancer. Over the past 20 years, increased understanding of the mechanism of action of 5-FU has led to the development of strategies that increase its anticancer activity. Despite these advances, drug resistance remains a significant limitation to the clinical use of 5-FU. Emerging technologies, such as DNA microarray profiling, have the potential to identify novel genes that are involved in mediating resistance to 5-FU. Such target genes might prove to be therapeutically valuable as new targets for chemotherapy, or as predictive biomarkers of response to 5-FU-based chemotherapy.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cancer Drug Resist
                Journal ID (iso-abbrev): Cancer Drug Resist
                Journal ID (publisher-id): CDR
                Title: Cancer Drug Resistance
                Publisher: OAE Publishing Inc.
                ISSN (Electronic): 2578-532X
                Publication date Collection: 2025
                Publication date (Electronic): 16 January 2025
                Volume: 8
                Electronic Location Identifier: 4
                Affiliations
                1Department of Pharmacology, West China School of Pharmacy, Sichuan University, Chengdu 610051, Sichuan, China.
                2Department of Nuclear Medicine, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu 610051, Sichuan, China.
                3State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou 510700, Guangdong, China.
                4Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Sichuan University, Chengdu 610041, Sichuan, China.
                Author notes
                Correspondence to: Dr. WenlingTu, Department of Nuclear Medicine, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, 4 north fourth section, Erhuan Rd, Chengdu 610051, Sichuan, China. E-mail: tu.wenling@ 123456foxmail.com ; Dr. Fu Peng, Department of Pharmacology, West China School of Pharmacy, Sichuan University, No. 17, Section 3, Southern Renmin Rd, Chengdu 610051, Sichuan, China. E-mail: pengf@ 123456scu.edu.cn

                Academic Editor: Erik A. C. Wiemer | Copy Editor: Ting-Ting Hu | Production Editor: Ting-Ting Hu

                Article
                DOI: 10.20517/cdr.2024.167
                PMC ID: 11810461
                SO-VID: 4cd7a66b-c663-4be0-8a84-218e2837dd1f
                Copyright © © The Author(s) 2025.
                License:

                © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Date received : 28 October 2024
                Date revision received : 29 December 2024
                Date accepted : 07 January 2025
                Funding
                Funded by: This work was supported by the Youth Talent Promotion Project of China Association for Science and Technology (No.CACM-2020-QNRC1-01), the National Interdisciplinary Innovation Team of Traditional Chinese Medicine (No.ZYYCXTD-D-202209), the Project of Science and Technology Department of Sichuan Province (Nos.2023NSFSC1928; 2023NSFSC1992), the Multidimensional Evaluation of Specialty Chinese Medicine Resources and Product Development Innovation Team (No.2022C001)
                Categories
                Subject: Review

                Keywords: non-coding rnas,5-fluorouracil,gastrointestinal cancers,chemoresistance,tumor microenvironment
                Data availability:
                Keywords: non-coding rnas, 5-fluorouracil, gastrointestinal cancers, chemoresistance, tumor microenvironment

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