The emerging roles of aberrant alternative splicing in glioma
Abstract Gliomas represent a heterogeneous group of uniformly fatal brain tumors. Low and high-grade gliomas have diverse molecular signatures. Despite successful advances in understanding glioma, several genetic, epigenetic, and post-transcriptional alterations leave various targeted therapies inef...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-02-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02323-0 |
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| _version_ | 1823863253958131712 |
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| author | Reda Ben Mrid Sara El Guendouzi Marco Mineo Rachid El Fatimy |
| author_facet | Reda Ben Mrid Sara El Guendouzi Marco Mineo Rachid El Fatimy |
| author_sort | Reda Ben Mrid |
| collection | DOAJ |
| description | Abstract Gliomas represent a heterogeneous group of uniformly fatal brain tumors. Low and high-grade gliomas have diverse molecular signatures. Despite successful advances in understanding glioma, several genetic, epigenetic, and post-transcriptional alterations leave various targeted therapies ineffective, leading to a poor prognosis for high-grade glioma. Recent advances have revealed the implication of dysregulated alternative splicing (AS) events in glioma development. AS is a process that produces, from a single genomic sequence, several mature messenger RNAs. Splicing of pre-messenger RNAs concerns at least 95% of transcripts and constitutes an important mechanism in gene expression regulation. Dysregulation of this process, through variations in spliceosome components, aberrant splicing factors and RNA-binding protein activity, disproportionate regulation of non-coding RNAs, and abnormal mRNA methylation, can contribute to the disruption of AS. Such disruptions are usually associated with the development of several cancers, including glioma. Consequently, AS constitutes a key regulatory mechanism that could serve as a target for future therapies. In this review, we explore how AS events, spliceosome components, and their regulatory mechanisms play a critical role in glioma development, highlighting their potential as targets for innovative therapeutic strategies against this challenging cancer. |
| format | Article |
| id | doaj-art-27f3eadc9fee49c09204ee5e7f6fa55c |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-27f3eadc9fee49c09204ee5e7f6fa55c2025-02-09T12:12:27ZengNature Publishing GroupCell Death Discovery2058-77162025-02-0111111110.1038/s41420-025-02323-0The emerging roles of aberrant alternative splicing in gliomaReda Ben Mrid0Sara El Guendouzi1Marco Mineo2Rachid El Fatimy3Institute of Biological Sciences (ISSB), Faculty of Medical Sciences, Mohammed VI Polytechnic University (FMS-UM6P)Institute of Biological Sciences (ISSB), Faculty of Medical Sciences, Mohammed VI Polytechnic University (FMS-UM6P)Harvey W. Cushing Neuro-oncology Laboratories, Department of Neurosurgery, Harvard Medical School and Brigham and Women’s HospitalInstitute of Biological Sciences (ISSB), Faculty of Medical Sciences, Mohammed VI Polytechnic University (FMS-UM6P)Abstract Gliomas represent a heterogeneous group of uniformly fatal brain tumors. Low and high-grade gliomas have diverse molecular signatures. Despite successful advances in understanding glioma, several genetic, epigenetic, and post-transcriptional alterations leave various targeted therapies ineffective, leading to a poor prognosis for high-grade glioma. Recent advances have revealed the implication of dysregulated alternative splicing (AS) events in glioma development. AS is a process that produces, from a single genomic sequence, several mature messenger RNAs. Splicing of pre-messenger RNAs concerns at least 95% of transcripts and constitutes an important mechanism in gene expression regulation. Dysregulation of this process, through variations in spliceosome components, aberrant splicing factors and RNA-binding protein activity, disproportionate regulation of non-coding RNAs, and abnormal mRNA methylation, can contribute to the disruption of AS. Such disruptions are usually associated with the development of several cancers, including glioma. Consequently, AS constitutes a key regulatory mechanism that could serve as a target for future therapies. In this review, we explore how AS events, spliceosome components, and their regulatory mechanisms play a critical role in glioma development, highlighting their potential as targets for innovative therapeutic strategies against this challenging cancer.https://doi.org/10.1038/s41420-025-02323-0 |
| spellingShingle | Reda Ben Mrid Sara El Guendouzi Marco Mineo Rachid El Fatimy The emerging roles of aberrant alternative splicing in glioma Cell Death Discovery |
| title | The emerging roles of aberrant alternative splicing in glioma |
| title_full | The emerging roles of aberrant alternative splicing in glioma |
| title_fullStr | The emerging roles of aberrant alternative splicing in glioma |
| title_full_unstemmed | The emerging roles of aberrant alternative splicing in glioma |
| title_short | The emerging roles of aberrant alternative splicing in glioma |
| title_sort | emerging roles of aberrant alternative splicing in glioma |
| url | https://doi.org/10.1038/s41420-025-02323-0 |
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