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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BMC
2025-08-01
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| Series: | Journal of Translational Medicine |
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| 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. |
| format | Article |
| id | doaj-art-5704ff6c207d4764814caa07260780fb |
| institution | DOAJ |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| 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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