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PRMT5 and CDK4/6 inhibition result in distinctive patterns of alternative splicing in melanoma
Drugs targeting cyclin-dependent kinases 4 and 6 (CDK4/6) are promising new treatments for melanoma and other solid malignancies. In studies on CDK4/6 inhibitor resistance, protein arginine methyltransferase 5 (PRMT5) regulation of alternative splicing was shown to be an important downstream compone...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621831/ https://www.ncbi.nlm.nih.gov/pubmed/37917641 http://dx.doi.org/10.1371/journal.pone.0292278 |
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author | Chan, Lok Hang Wang, Peihan Abuhammad, Shatha Lim, Lydia Rui Jia Cursons, Joseph Sheppard, Karen E. Goode, David L. |
author_facet | Chan, Lok Hang Wang, Peihan Abuhammad, Shatha Lim, Lydia Rui Jia Cursons, Joseph Sheppard, Karen E. Goode, David L. |
author_sort | Chan, Lok Hang |
collection | PubMed |
description | Drugs targeting cyclin-dependent kinases 4 and 6 (CDK4/6) are promising new treatments for melanoma and other solid malignancies. In studies on CDK4/6 inhibitor resistance, protein arginine methyltransferase 5 (PRMT5) regulation of alternative splicing was shown to be an important downstream component of the CDK4/6 pathway. However, the full effects of inhibition of CDK4/6 on splicing events in melanoma and the extent to which they are dependent on PRMT5 has not been established. We performed full-length mRNA sequencing on CHL1 and A375 melanoma cell lines treated with the CDK4/6 inhibitor palbociclib and the PRMT5 inhibitor GSK3326595 and analysed data for differential gene expression and differential pre-mRNA splicing induced by these agents. Changes in gene expression and RNA splicing were more extensive under PRMT5 inhibition than under CDK4/6 inhibition. Although PRMT5 inhibition and CDK4/6 inhibition induced common RNA splicing events and gene expression profiles, the majority of events induced by CDK4/6 inhibition were distinct. Our findings indicate CDK4/6 has the ability to regulate alternative splicing in a manner that is distinct from PRMT5 inhibition, resulting in divergent changes in gene expression under each therapy. |
format | Online Article Text |
id | pubmed-10621831 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-106218312023-11-03 PRMT5 and CDK4/6 inhibition result in distinctive patterns of alternative splicing in melanoma Chan, Lok Hang Wang, Peihan Abuhammad, Shatha Lim, Lydia Rui Jia Cursons, Joseph Sheppard, Karen E. Goode, David L. PLoS One Research Article Drugs targeting cyclin-dependent kinases 4 and 6 (CDK4/6) are promising new treatments for melanoma and other solid malignancies. In studies on CDK4/6 inhibitor resistance, protein arginine methyltransferase 5 (PRMT5) regulation of alternative splicing was shown to be an important downstream component of the CDK4/6 pathway. However, the full effects of inhibition of CDK4/6 on splicing events in melanoma and the extent to which they are dependent on PRMT5 has not been established. We performed full-length mRNA sequencing on CHL1 and A375 melanoma cell lines treated with the CDK4/6 inhibitor palbociclib and the PRMT5 inhibitor GSK3326595 and analysed data for differential gene expression and differential pre-mRNA splicing induced by these agents. Changes in gene expression and RNA splicing were more extensive under PRMT5 inhibition than under CDK4/6 inhibition. Although PRMT5 inhibition and CDK4/6 inhibition induced common RNA splicing events and gene expression profiles, the majority of events induced by CDK4/6 inhibition were distinct. Our findings indicate CDK4/6 has the ability to regulate alternative splicing in a manner that is distinct from PRMT5 inhibition, resulting in divergent changes in gene expression under each therapy. Public Library of Science 2023-11-02 /pmc/articles/PMC10621831/ /pubmed/37917641 http://dx.doi.org/10.1371/journal.pone.0292278 Text en © 2023 Chan et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Chan, Lok Hang Wang, Peihan Abuhammad, Shatha Lim, Lydia Rui Jia Cursons, Joseph Sheppard, Karen E. Goode, David L. PRMT5 and CDK4/6 inhibition result in distinctive patterns of alternative splicing in melanoma |
title | PRMT5 and CDK4/6 inhibition result in distinctive patterns of alternative splicing in melanoma |
title_full | PRMT5 and CDK4/6 inhibition result in distinctive patterns of alternative splicing in melanoma |
title_fullStr | PRMT5 and CDK4/6 inhibition result in distinctive patterns of alternative splicing in melanoma |
title_full_unstemmed | PRMT5 and CDK4/6 inhibition result in distinctive patterns of alternative splicing in melanoma |
title_short | PRMT5 and CDK4/6 inhibition result in distinctive patterns of alternative splicing in melanoma |
title_sort | prmt5 and cdk4/6 inhibition result in distinctive patterns of alternative splicing in melanoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10621831/ https://www.ncbi.nlm.nih.gov/pubmed/37917641 http://dx.doi.org/10.1371/journal.pone.0292278 |
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