The translatome of glioblastoma
Glioblastoma (GB), the most common and aggressive brain tumor, demonstrates intrinsic resistance to current therapies, resulting in poor clinical outcomes. Cancer progression can be partially attributed to the deregulation of protein translation mechanisms that drive cancer cell growth. In this stud...
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| Format: | Article |
| Language: | English |
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Wiley
2025-03-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.13743 |
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| author | Fleur M. G. Cornelissen Zhaoren He Edward Ciputra Richard R. deHaas Ammarina Beumer‐Chuwonpad David Noske W. Peter Vandertop Sander R. Piersma Connie R. Jiménez Cornelis Murre Bart A. Westerman |
| author_facet | Fleur M. G. Cornelissen Zhaoren He Edward Ciputra Richard R. deHaas Ammarina Beumer‐Chuwonpad David Noske W. Peter Vandertop Sander R. Piersma Connie R. Jiménez Cornelis Murre Bart A. Westerman |
| author_sort | Fleur M. G. Cornelissen |
| collection | DOAJ |
| description | Glioblastoma (GB), the most common and aggressive brain tumor, demonstrates intrinsic resistance to current therapies, resulting in poor clinical outcomes. Cancer progression can be partially attributed to the deregulation of protein translation mechanisms that drive cancer cell growth. In this study, we present the translatome landscape of GB as a valuable data resource. Eight patient‐derived GB sphere cultures (GSCs) were analyzed using ribosome profiling and messenger RNA (mRNA) sequencing. We investigated inter‐cell‐line differences through differential expression analysis at both the translatome and transcriptome levels. Translational changes post‐radiotherapy were assessed at 30 and 60 min. The translation of non‐coding RNAs (ncRNAs) was validated using in‐house and public mass spectrometry (MS) data, whereas RNA expression was confirmed by quantitative PCR (qPCR). Our findings demonstrate that ribosome sequencing provides more detailed information than MS or transcriptional analyses. Transcriptional similarities among GSCs correlate with translational similarities, aligning with previously defined subtypes such as proneural and mesenchymal. Additionally, we identified a broad spectrum of open reading frame types in both coding and non‐coding mRNA regions, including long non‐coding RNAs (lncRNAs) and pseudogenes undergoing active translation. Translation of ncRNAs into peptides was independently confirmed by in‐house data and external MS data. We also observed that translational regulation of histones (downregulated) and splicing factors (upregulated) occurs in response to radiotherapy. These data offer new insights into genome‐wide protein synthesis, identifying translationally regulated genes and alternative translation initiation sites in GB under normal and radiotherapeutic conditions, providing a rich resource for GB research. Further functional validation of differentially expressed genes after radiotherapy is needed. Understanding translational control in GB can reveal mechanistic insights and identify currently unknown biomarkers, ultimately enhancing the diagnosis and treatment of this aggressive brain cancer. |
| format | Article |
| id | doaj-art-323a0cea2a8841f886661e831dd2b8d9 |
| institution | DOAJ |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-323a0cea2a8841f886661e831dd2b8d92025-08-20T02:59:42ZengWileyMolecular Oncology1574-78911878-02612025-03-0119371674010.1002/1878-0261.13743The translatome of glioblastomaFleur M. G. Cornelissen0Zhaoren He1Edward Ciputra2Richard R. deHaas3Ammarina Beumer‐Chuwonpad4David Noske5W. Peter Vandertop6Sander R. Piersma7Connie R. Jiménez8Cornelis Murre9Bart A. Westerman10Department of Molecular Biology University of California, San Diego La Jolla CA USADepartment of Molecular Biology University of California, San Diego La Jolla CA USADepartment of Neurosurgery Amsterdam UMC, Location VUMC, Cancer Center Amsterdam The NetherlandsOncoProteomics Laboratory, Cancer Center Amsterdam Amsterdam UMC The NetherlandsDepartment of Neurosurgery Amsterdam UMC, Location VUMC, Cancer Center Amsterdam The NetherlandsDepartment of Neurosurgery Amsterdam UMC, Location VUMC, Cancer Center Amsterdam The NetherlandsDepartment of Neurosurgery Amsterdam UMC, Location VUMC, Cancer Center Amsterdam The NetherlandsOncoProteomics Laboratory, Cancer Center Amsterdam Amsterdam UMC The NetherlandsOncoProteomics Laboratory, Cancer Center Amsterdam Amsterdam UMC The NetherlandsDepartment of Molecular Biology University of California, San Diego La Jolla CA USADepartment of Neurosurgery Amsterdam UMC, Location VUMC, Cancer Center Amsterdam The NetherlandsGlioblastoma (GB), the most common and aggressive brain tumor, demonstrates intrinsic resistance to current therapies, resulting in poor clinical outcomes. Cancer progression can be partially attributed to the deregulation of protein translation mechanisms that drive cancer cell growth. In this study, we present the translatome landscape of GB as a valuable data resource. Eight patient‐derived GB sphere cultures (GSCs) were analyzed using ribosome profiling and messenger RNA (mRNA) sequencing. We investigated inter‐cell‐line differences through differential expression analysis at both the translatome and transcriptome levels. Translational changes post‐radiotherapy were assessed at 30 and 60 min. The translation of non‐coding RNAs (ncRNAs) was validated using in‐house and public mass spectrometry (MS) data, whereas RNA expression was confirmed by quantitative PCR (qPCR). Our findings demonstrate that ribosome sequencing provides more detailed information than MS or transcriptional analyses. Transcriptional similarities among GSCs correlate with translational similarities, aligning with previously defined subtypes such as proneural and mesenchymal. Additionally, we identified a broad spectrum of open reading frame types in both coding and non‐coding mRNA regions, including long non‐coding RNAs (lncRNAs) and pseudogenes undergoing active translation. Translation of ncRNAs into peptides was independently confirmed by in‐house data and external MS data. We also observed that translational regulation of histones (downregulated) and splicing factors (upregulated) occurs in response to radiotherapy. These data offer new insights into genome‐wide protein synthesis, identifying translationally regulated genes and alternative translation initiation sites in GB under normal and radiotherapeutic conditions, providing a rich resource for GB research. Further functional validation of differentially expressed genes after radiotherapy is needed. Understanding translational control in GB can reveal mechanistic insights and identify currently unknown biomarkers, ultimately enhancing the diagnosis and treatment of this aggressive brain cancer.https://doi.org/10.1002/1878-0261.13743glioblastomanon‐coding RNAradioresistanceradiotherapytranslatome |
| spellingShingle | Fleur M. G. Cornelissen Zhaoren He Edward Ciputra Richard R. deHaas Ammarina Beumer‐Chuwonpad David Noske W. Peter Vandertop Sander R. Piersma Connie R. Jiménez Cornelis Murre Bart A. Westerman The translatome of glioblastoma Molecular Oncology glioblastoma non‐coding RNA radioresistance radiotherapy translatome |
| title | The translatome of glioblastoma |
| title_full | The translatome of glioblastoma |
| title_fullStr | The translatome of glioblastoma |
| title_full_unstemmed | The translatome of glioblastoma |
| title_short | The translatome of glioblastoma |
| title_sort | translatome of glioblastoma |
| topic | glioblastoma non‐coding RNA radioresistance radiotherapy translatome |
| url | https://doi.org/10.1002/1878-0261.13743 |
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