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Reinvestigating the clinical relevance of the m(6)A writer METTL3 in urothelial carcinoma of the bladder
METTL3 is the major writer of N6-Methyladenosine (m(6)A) and has been associated with controversial roles in cancer. This is best illustrated in urothelial carcinoma of the bladder (UCB), where METTL3 was described to have both oncogenic and tumor-suppressive functions. Here, we reinvestigated the r...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10405067/ https://www.ncbi.nlm.nih.gov/pubmed/37554463 http://dx.doi.org/10.1016/j.isci.2023.107300 |
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author | Koch, Jonas Neuberger, Manuel Schmidt-Dengler, Martina Xu, Jinyun Carneiro, Vitor Coutinho Ellinger, Jörg Kriegmair, Maximilian C. Nuhn, Philipp Erben, Philipp Michel, Maurice Stephan Helm, Mark Rodríguez-Paredes, Manuel Nientiedt, Malin Lyko, Frank |
author_facet | Koch, Jonas Neuberger, Manuel Schmidt-Dengler, Martina Xu, Jinyun Carneiro, Vitor Coutinho Ellinger, Jörg Kriegmair, Maximilian C. Nuhn, Philipp Erben, Philipp Michel, Maurice Stephan Helm, Mark Rodríguez-Paredes, Manuel Nientiedt, Malin Lyko, Frank |
author_sort | Koch, Jonas |
collection | PubMed |
description | METTL3 is the major writer of N6-Methyladenosine (m(6)A) and has been associated with controversial roles in cancer. This is best illustrated in urothelial carcinoma of the bladder (UCB), where METTL3 was described to have both oncogenic and tumor-suppressive functions. Here, we reinvestigated the role of METTL3 in UCB. METTL3 knockout reduced the oncogenic phenotype and m(6)A levels of UCB cell lines. However, complete depletion of METTL3/m(6)A was not achieved due to selection of cells expressing alternative METTL3 isoforms. Systematic vulnerability and inhibitor response analyses suggested that uroepithelial cells depend on METTL3 for viability. Furthermore, expression and survival analyses of clinical data revealed a complex role for METTL3 in UCB, with decreased m(6)A mRNA levels in UCB tumors. Our results suggest that METTL3 expression may be a suitable diagnostic UCB biomarker, as the enzyme promotes UCB formation. However, the suitability of the enzyme as a therapeutic target should be evaluated carefully. |
format | Online Article Text |
id | pubmed-10405067 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-104050672023-08-08 Reinvestigating the clinical relevance of the m(6)A writer METTL3 in urothelial carcinoma of the bladder Koch, Jonas Neuberger, Manuel Schmidt-Dengler, Martina Xu, Jinyun Carneiro, Vitor Coutinho Ellinger, Jörg Kriegmair, Maximilian C. Nuhn, Philipp Erben, Philipp Michel, Maurice Stephan Helm, Mark Rodríguez-Paredes, Manuel Nientiedt, Malin Lyko, Frank iScience Article METTL3 is the major writer of N6-Methyladenosine (m(6)A) and has been associated with controversial roles in cancer. This is best illustrated in urothelial carcinoma of the bladder (UCB), where METTL3 was described to have both oncogenic and tumor-suppressive functions. Here, we reinvestigated the role of METTL3 in UCB. METTL3 knockout reduced the oncogenic phenotype and m(6)A levels of UCB cell lines. However, complete depletion of METTL3/m(6)A was not achieved due to selection of cells expressing alternative METTL3 isoforms. Systematic vulnerability and inhibitor response analyses suggested that uroepithelial cells depend on METTL3 for viability. Furthermore, expression and survival analyses of clinical data revealed a complex role for METTL3 in UCB, with decreased m(6)A mRNA levels in UCB tumors. Our results suggest that METTL3 expression may be a suitable diagnostic UCB biomarker, as the enzyme promotes UCB formation. However, the suitability of the enzyme as a therapeutic target should be evaluated carefully. Elsevier 2023-07-11 /pmc/articles/PMC10405067/ /pubmed/37554463 http://dx.doi.org/10.1016/j.isci.2023.107300 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Koch, Jonas Neuberger, Manuel Schmidt-Dengler, Martina Xu, Jinyun Carneiro, Vitor Coutinho Ellinger, Jörg Kriegmair, Maximilian C. Nuhn, Philipp Erben, Philipp Michel, Maurice Stephan Helm, Mark Rodríguez-Paredes, Manuel Nientiedt, Malin Lyko, Frank Reinvestigating the clinical relevance of the m(6)A writer METTL3 in urothelial carcinoma of the bladder |
title | Reinvestigating the clinical relevance of the m(6)A writer METTL3 in urothelial carcinoma of the bladder |
title_full | Reinvestigating the clinical relevance of the m(6)A writer METTL3 in urothelial carcinoma of the bladder |
title_fullStr | Reinvestigating the clinical relevance of the m(6)A writer METTL3 in urothelial carcinoma of the bladder |
title_full_unstemmed | Reinvestigating the clinical relevance of the m(6)A writer METTL3 in urothelial carcinoma of the bladder |
title_short | Reinvestigating the clinical relevance of the m(6)A writer METTL3 in urothelial carcinoma of the bladder |
title_sort | reinvestigating the clinical relevance of the m(6)a writer mettl3 in urothelial carcinoma of the bladder |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10405067/ https://www.ncbi.nlm.nih.gov/pubmed/37554463 http://dx.doi.org/10.1016/j.isci.2023.107300 |
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