Mechanistic insights into the role of RNA demethylase ALKBH5 in malignant tumor therapy

Abstract m6A RNA methylation represents the most prevalent epitranscriptomic modification and modulates diverse dimensions of RNA metabolism. As a dynamic and reversible post-transcriptional mark, m6A is broadly distributed across multiple RNA types, including mRNA, ribosomal RNA (rRNA), microRNA (m...

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Main Authors: Ruijie An, Yingjie Shao, Wendong Gu
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-025-06938-w
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author Ruijie An
Yingjie Shao
Wendong Gu
author_facet Ruijie An
Yingjie Shao
Wendong Gu
author_sort Ruijie An
collection DOAJ
description Abstract m6A RNA methylation represents the most prevalent epitranscriptomic modification and modulates diverse dimensions of RNA metabolism. As a dynamic and reversible post-transcriptional mark, m6A is broadly distributed across multiple RNA types, including mRNA, ribosomal RNA (rRNA), microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA), and small nuclear RNA (snRNA). ALKB homolog 5 (ALKBH5), an m6A demethylase, has been extensively characterized for its involvement in tumorigenesis and progression through the removal of methylated modification from RNA, subsequently influencing RNA metabolism and gene expression regulation. A growing body of evidence indicates that ALKBH5 contributes to the therapeutic response in various cancers. Its aberrant expression is frequently observed across malignancies, where it modulates oncoprotein levels, promotes tumor initiation, and accelerates cancer cell proliferation, progression, and metastasis. Nevertheless, its implications for therapy responsiveness and the emergence of drug resistance remain poorly understood. This review centers on ALKBH5-mediated regulatory pathways and mechanisms in the contexts of chemotherapy, radiotherapy, and immunotherapy in malignancies, while also evaluating the therapeutic relevance of ALKBH5 as a molecular target and the potential of its pharmacological inhibitors.
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spelling doaj-art-5704ff6c207d4764814caa07260780fb2025-08-20T03:05:57ZengBMCJournal of Translational Medicine1479-58762025-08-0123111410.1186/s12967-025-06938-wMechanistic insights into the role of RNA demethylase ALKBH5 in malignant tumor therapyRuijie An0Yingjie Shao1Wendong Gu2Department of Radiation Oncology, The Third Affiliated Hospital of Soochow UniversityDepartment of Radiation Oncology, The Third Affiliated Hospital of Soochow UniversityDepartment of Radiation Oncology, The Third Affiliated Hospital of Soochow UniversityAbstract m6A RNA methylation represents the most prevalent epitranscriptomic modification and modulates diverse dimensions of RNA metabolism. As a dynamic and reversible post-transcriptional mark, m6A is broadly distributed across multiple RNA types, including mRNA, ribosomal RNA (rRNA), microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA), and small nuclear RNA (snRNA). ALKB homolog 5 (ALKBH5), an m6A demethylase, has been extensively characterized for its involvement in tumorigenesis and progression through the removal of methylated modification from RNA, subsequently influencing RNA metabolism and gene expression regulation. A growing body of evidence indicates that ALKBH5 contributes to the therapeutic response in various cancers. Its aberrant expression is frequently observed across malignancies, where it modulates oncoprotein levels, promotes tumor initiation, and accelerates cancer cell proliferation, progression, and metastasis. Nevertheless, its implications for therapy responsiveness and the emergence of drug resistance remain poorly understood. This review centers on ALKBH5-mediated regulatory pathways and mechanisms in the contexts of chemotherapy, radiotherapy, and immunotherapy in malignancies, while also evaluating the therapeutic relevance of ALKBH5 as a molecular target and the potential of its pharmacological inhibitors.https://doi.org/10.1186/s12967-025-06938-wALKBH5m6A methylationCisplatinRadiosensitivityPD-L1
spellingShingle Ruijie An
Yingjie Shao
Wendong Gu
Mechanistic insights into the role of RNA demethylase ALKBH5 in malignant tumor therapy
Journal of Translational Medicine
ALKBH5
m6A methylation
Cisplatin
Radiosensitivity
PD-L1
title Mechanistic insights into the role of RNA demethylase ALKBH5 in malignant tumor therapy
title_full Mechanistic insights into the role of RNA demethylase ALKBH5 in malignant tumor therapy
title_fullStr Mechanistic insights into the role of RNA demethylase ALKBH5 in malignant tumor therapy
title_full_unstemmed Mechanistic insights into the role of RNA demethylase ALKBH5 in malignant tumor therapy
title_short Mechanistic insights into the role of RNA demethylase ALKBH5 in malignant tumor therapy
title_sort mechanistic insights into the role of rna demethylase alkbh5 in malignant tumor therapy
topic ALKBH5
m6A methylation
Cisplatin
Radiosensitivity
PD-L1
url https://doi.org/10.1186/s12967-025-06938-w
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AT wendonggu mechanisticinsightsintotheroleofrnademethylasealkbh5inmalignanttumortherapy