Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Cyclin-dependent kinase 9 (CDK9) phosphorylates RNA polymerase II to promote productive transcription elongation. Here we show that short-term CDK9 inhibition affects the splicing of thousands of mRNAs. CDK9 inhibition impairs global splicing and there is no evidence for a coordinated response between the alternative splicing and the overall transcriptome. Alternative splicing is a feature of aggressive prostate cancer (CRPC) and enables the generation of the anti-androgen resistant version of the ligand-independent androgen receptor, AR-v7. We show that CDK9 inhibition results in the loss of AR and AR-v7 expression due to the defects in splicing, which sensitizes CRPC cells to androgen deprivation. Finally, we demonstrate that CDK9 expression increases as PC cells develop CRPC-phenotype both in vitro and also in patient samples. To conclude, here we show that CDK9 inhibition compromises splicing in PC cells, which can be capitalized on by targeting the PC-specific addiction androgen receptor.

Original publication

DOI

10.1080/15476286.2021.1983287

Type

Journal article

Journal

RNA Biol

Publication Date

12/11/2021

Volume

18

Pages

722 - 729

Keywords

Cyclin-dependent kinase 9, bioinformatics, o-glcnac transferase, prostate cancer, splicing, Alternative Splicing, Cell Line, Tumor, Cyclin-Dependent Kinase 9, Enzyme Activation, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Male, Oligonucleotides, Prostatic Neoplasms, Protein Kinase Inhibitors, RNA Interference, RNA Splicing, RNA, Messenger, Receptors, Androgen, Spliceosomes