111614
论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
- 3.4 Breast Cancer (Dove Med Press)
- 3.2 Clin Epidemiol
- 2.6 Cancer Manag Res
- 2.9 Infect Drug Resist
- 3.7 Clin Interv Aging
- 5.1 Drug Des Dev Ther
- 3.1 Int J Chronic Obstr
- 6.6 Int J Nanomed
- 2.6 Int J Women's Health
- 2.9 Neuropsych Dis Treat
- 2.8 OncoTargets Ther
- 2.0 Patient Prefer Adher
- 2.2 Ther Clin Risk Manag
- 2.5 J Pain Res
- 3.0 Diabet Metab Synd Ob
- 3.2 Psychol Res Behav Ma
- 3.4 Nat Sci Sleep
- 1.8 Pharmgenomics Pers Med
- 2.0 Risk Manag Healthc Policy
- 4.1 J Inflamm Res
- 2.0 Int J Gen Med
- 3.4 J Hepatocell Carcinoma
- 3.0 J Asthma Allergy
- 2.2 Clin Cosmet Investig Dermatol
- 2.4 J Multidiscip Healthc
已发表论文
YTHDC1-m6A-MEG3 调控轴在放射性肝损伤中的作用：解析早期表观转录组学改变及分子动态
Authors Guo CY , Du YF, Yan HCHC , Tian FQ , Xu P
Received 5 June 2025
Accepted for publication 3 November 2025
Published 27 November 2025 Volume 2025:18 Pages 16611—16618
DOI https://doi.org/10.2147/JIR.S536310
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Fatih Türker
Cun-yang Guo,1,2,* Yi-fei Du,1,2,* Hui-cong Yan,1,3 Fang-qi Tian,1 Ping Xu1
1Laboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, 277160, People’s Republic of China; 2School of Public Health, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China; 3School of Public Health, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Ping Xu, Email 19863349848@163.com
Abstract: Radiation-induced liver injury (RILI) remains one of the most severe complications encountered during radiotherapy for hepatocellular carcinoma (HCC), cholangiocarcinoma, and tumors of the right lower lung. Although clinically significant, the molecular mechanisms that drive RILI are still incompletely understood. In our recent study published in Cell Death and Disease, entitled “The YTHDC1 Reader Protein Recognizes and Regulates the lncRNA MEG3 Following Its METTL3-Mediated m6A Methylation: A Novel Mechanism Early During RILI”, we investigated in depth the epitranscriptomic regulation of RILI pathogenesis. Post-irradiation, the disease progresses in a staged manner: an early phase characterized by hepatocyte apoptosis and inflammatory activation, a subsequent stage dominated by fibrotic remodeling, and ultimately leading to liver failure. The absence of reliable early biomarkers severely limits timely diagnosis and therapeutic intervention. Among potential candidates, RNA modifications such as N6-methyladenosine (m6A) have emerged as key modulators of cellular stress responses and early pathogenic mechanisms, holding promise as novel diagnostic or therapeutic targets. As a major regulator of RNA metabolism, m6A influences transcript splicing, stability, and translation through the orchestrated actions of classes of proteins known as writers, erasers, and readers. This regulatory layer not only contributes to fundamental processes including DNA repair and inflammatory signaling but also shapes pathological changes via the modulation of lncRNA-chromatin interactions, highlighting its promise for therapeutic exploitation in cancer and RILI. In our study, we identified the long non-coding RNA MEG3 as a pivotal player in RILI, where it promotes apoptosis, drives inflammatory response, and accelerates fibrosis. We further demonstrated that MEG3 expression is tightly controlled by the METTL3-YTHDC1 axis, and YTHDC1-mediated recognition of m6A-modified MEG3 is essential for the progression of RILI. These insights establish the YTHDC1-MEG3 pathway as a key molecular driver of RILI and provide a framework for the design of targeted therapies to mitigate RILI.
Keywords: m6A methylation, lncRNA MEG3, RILI, METTL3-YTHDC1 axis, miR-20b/BNIP2
1Laboratory of Radiation-Induced Diseases and Molecule-Targeted Drugs, School of Food and Biomedicine, Zaozhuang University, Zaozhuang, Shandong, 277160, People’s Republic of China; 2School of Public Health, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China; 3School of Public Health, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Ping Xu, Email 19863349848@163.com
Abstract: Radiation-induced liver injury (RILI) remains one of the most severe complications encountered during radiotherapy for hepatocellular carcinoma (HCC), cholangiocarcinoma, and tumors of the right lower lung. Although clinically significant, the molecular mechanisms that drive RILI are still incompletely understood. In our recent study published in Cell Death and Disease, entitled “The YTHDC1 Reader Protein Recognizes and Regulates the lncRNA MEG3 Following Its METTL3-Mediated m6A Methylation: A Novel Mechanism Early During RILI”, we investigated in depth the epitranscriptomic regulation of RILI pathogenesis. Post-irradiation, the disease progresses in a staged manner: an early phase characterized by hepatocyte apoptosis and inflammatory activation, a subsequent stage dominated by fibrotic remodeling, and ultimately leading to liver failure. The absence of reliable early biomarkers severely limits timely diagnosis and therapeutic intervention. Among potential candidates, RNA modifications such as N6-methyladenosine (m6A) have emerged as key modulators of cellular stress responses and early pathogenic mechanisms, holding promise as novel diagnostic or therapeutic targets. As a major regulator of RNA metabolism, m6A influences transcript splicing, stability, and translation through the orchestrated actions of classes of proteins known as writers, erasers, and readers. This regulatory layer not only contributes to fundamental processes including DNA repair and inflammatory signaling but also shapes pathological changes via the modulation of lncRNA-chromatin interactions, highlighting its promise for therapeutic exploitation in cancer and RILI. In our study, we identified the long non-coding RNA MEG3 as a pivotal player in RILI, where it promotes apoptosis, drives inflammatory response, and accelerates fibrosis. We further demonstrated that MEG3 expression is tightly controlled by the METTL3-YTHDC1 axis, and YTHDC1-mediated recognition of m6A-modified MEG3 is essential for the progression of RILI. These insights establish the YTHDC1-MEG3 pathway as a key molecular driver of RILI and provide a framework for the design of targeted therapies to mitigate RILI.
Keywords: m6A methylation, lncRNA MEG3, RILI, METTL3-YTHDC1 axis, miR-20b/BNIP2