RNA cytosine methyltransferase NSUN5 promotes protein synthesis and tumorigenic phenotypes in glioblastoma
Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. The standard treatment achieves a median overall survival for GBM patients of only 15 months. Hence, novel therapies based on an increased understanding of the mechanistic underpinnings of GBM are desperate...
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-09-01
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| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13434 |
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| author | Jiesi Zhou Yan Shu Kong Krista M. Vincent Dylan Dieters‐Castator Amirali B. Bukhari Darryl Glubrecht Rong‐Zong Liu Douglas Quilty Scott D. Findlay Xiaowei Huang Zhihua Xu Rui Zhe Yang Lanyue Zhang Emily Tang Gilles Lajoie David D. Eisenstat Armin M. Gamper Richard Fahlman Roseline Godbout Lynne‐Marie Postovit YangXin Fu |
| author_facet | Jiesi Zhou Yan Shu Kong Krista M. Vincent Dylan Dieters‐Castator Amirali B. Bukhari Darryl Glubrecht Rong‐Zong Liu Douglas Quilty Scott D. Findlay Xiaowei Huang Zhihua Xu Rui Zhe Yang Lanyue Zhang Emily Tang Gilles Lajoie David D. Eisenstat Armin M. Gamper Richard Fahlman Roseline Godbout Lynne‐Marie Postovit YangXin Fu |
| author_sort | Jiesi Zhou |
| collection | DOAJ |
| description | Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. The standard treatment achieves a median overall survival for GBM patients of only 15 months. Hence, novel therapies based on an increased understanding of the mechanistic underpinnings of GBM are desperately needed. In this study, we show that elevated expression of 28S rRNA (cytosine‐C(5))‐methyltransferase NSUN5, which methylates cytosine 3782 of 28S rRNA in GBM cells, is strongly associated with the poor survival of GBM patients. Moreover, we demonstrate that overexpression of NSUN5 increases protein synthesis in GBM cells. NSUN5 knockdown decreased protein synthesis, cell proliferation, sphere formation, migration, and resistance to temozolomide in GBM cell lines. NSUN5 knockdown also decreased the number and size of GBM neurospheres in vitro. As a corollary, mice harboring U251 tumors wherein NSUN5 was knocked down survived longer than mice harboring control tumors. Taken together, our results suggest that NSUN5 plays a protumorigenic role in GBM by enabling the enhanced protein synthesis requisite for tumor progression. Accordingly, NSUN5 may be a hitherto unappreciated target for the treatment of GBM. |
| first_indexed | 2024-03-12T02:02:20Z |
| format | Article |
| id | doaj.art-919b27202fed43f09567395980a0f763 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-03-12T02:02:20Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-919b27202fed43f09567395980a0f7632023-09-07T10:57:03ZengWileyMolecular Oncology1574-78911878-02612023-09-011791763178310.1002/1878-0261.13434RNA cytosine methyltransferase NSUN5 promotes protein synthesis and tumorigenic phenotypes in glioblastomaJiesi Zhou0Yan Shu Kong1Krista M. Vincent2Dylan Dieters‐Castator3Amirali B. Bukhari4Darryl Glubrecht5Rong‐Zong Liu6Douglas Quilty7Scott D. Findlay8Xiaowei Huang9Zhihua Xu10Rui Zhe Yang11Lanyue Zhang12Emily Tang13Gilles Lajoie14David D. Eisenstat15Armin M. Gamper16Richard Fahlman17Roseline Godbout18Lynne‐Marie Postovit19YangXin Fu20Department of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Biochemistry Western University London ON CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Biochemistry Western University London ON CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Biochemistry, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaDepartment of Oncology, Faculty of Medicine and Dentistry University of Alberta Edmonton AB CanadaGlioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. The standard treatment achieves a median overall survival for GBM patients of only 15 months. Hence, novel therapies based on an increased understanding of the mechanistic underpinnings of GBM are desperately needed. In this study, we show that elevated expression of 28S rRNA (cytosine‐C(5))‐methyltransferase NSUN5, which methylates cytosine 3782 of 28S rRNA in GBM cells, is strongly associated with the poor survival of GBM patients. Moreover, we demonstrate that overexpression of NSUN5 increases protein synthesis in GBM cells. NSUN5 knockdown decreased protein synthesis, cell proliferation, sphere formation, migration, and resistance to temozolomide in GBM cell lines. NSUN5 knockdown also decreased the number and size of GBM neurospheres in vitro. As a corollary, mice harboring U251 tumors wherein NSUN5 was knocked down survived longer than mice harboring control tumors. Taken together, our results suggest that NSUN5 plays a protumorigenic role in GBM by enabling the enhanced protein synthesis requisite for tumor progression. Accordingly, NSUN5 may be a hitherto unappreciated target for the treatment of GBM.https://doi.org/10.1002/1878-0261.13434glioblastomaNSUN5protein synthesisRNA cytosine methylation |
| spellingShingle | Jiesi Zhou Yan Shu Kong Krista M. Vincent Dylan Dieters‐Castator Amirali B. Bukhari Darryl Glubrecht Rong‐Zong Liu Douglas Quilty Scott D. Findlay Xiaowei Huang Zhihua Xu Rui Zhe Yang Lanyue Zhang Emily Tang Gilles Lajoie David D. Eisenstat Armin M. Gamper Richard Fahlman Roseline Godbout Lynne‐Marie Postovit YangXin Fu RNA cytosine methyltransferase NSUN5 promotes protein synthesis and tumorigenic phenotypes in glioblastoma Molecular Oncology glioblastoma NSUN5 protein synthesis RNA cytosine methylation |
| title | RNA cytosine methyltransferase NSUN5 promotes protein synthesis and tumorigenic phenotypes in glioblastoma |
| title_full | RNA cytosine methyltransferase NSUN5 promotes protein synthesis and tumorigenic phenotypes in glioblastoma |
| title_fullStr | RNA cytosine methyltransferase NSUN5 promotes protein synthesis and tumorigenic phenotypes in glioblastoma |
| title_full_unstemmed | RNA cytosine methyltransferase NSUN5 promotes protein synthesis and tumorigenic phenotypes in glioblastoma |
| title_short | RNA cytosine methyltransferase NSUN5 promotes protein synthesis and tumorigenic phenotypes in glioblastoma |
| title_sort | rna cytosine methyltransferase nsun5 promotes protein synthesis and tumorigenic phenotypes in glioblastoma |
| topic | glioblastoma NSUN5 protein synthesis RNA cytosine methylation |
| url | https://doi.org/10.1002/1878-0261.13434 |
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