PRMT5 and CDK4/6 inhibition result in distinctive patterns of alternative splicing in melanoma
- Author(s)
- Chan, LH; Wang, P; Abuhammad, S; Lim, LRJ; Cursons, J; Sheppard, KE; Goode, DL;
- Details
- Publication Year 2023,Volume 18,Issue #11,Page e0292278
- Journal Title
- PLoS One
- Publication Type
- Research article
- Abstract
- 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.
- Publisher
- PLOS
- Keywords
- Humans; *Alternative Splicing; Protein-Arginine N-Methyltransferases/metabolism; Cell Line, Tumor; *Melanoma/drug therapy/genetics/metabolism; RNA Splicing; Cyclin-Dependent Kinase 4/genetics/metabolism
- Department(s)
- Laboratory Research
- PubMed ID
- 37917641
- Publisher's Version
- https://doi.org/10.1371/journal.pone.0292278
- Open Access at Publisher's Site
https://doi.org/10.1371/journal.pone.0292278- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-12-11 11:25:08
Last Modified: 2023-12-11 11:28:19