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Inhibition of CDK9 activity compromises global splicing in prostate cancer cells

Qiang Hu1, Ninu Poulose2, Samuel Girmay3

  • 1Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.

RNA Biology
|October 1, 2021
PubMed

Insights

Short-term inhibition of cyclin-dependent kinase 9 (CDK9) impairs splicing in prostate cancer cells. This CDK9 inhibition reduces androgen receptor variants, sensitizing cancer to treatment.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Transcriptional Regulation

Background:

  • Cyclin-dependent kinase 9 (CDK9) is crucial for transcription elongation by phosphorylating RNA polymerase II.
  • Alternative splicing, particularly the generation of AR-v7, is linked to aggressive prostate cancer (CRPC) and anti-androgen resistance.

Purpose of the Study:

  • To investigate the impact of short-term CDK9 inhibition on mRNA splicing in prostate cancer.
  • To determine if CDK9 inhibition affects AR and AR-v7 expression and sensitizes CRPC cells to treatment.

Main Methods:

  • CDK9 inhibition in prostate cancer cells.
  • Analysis of global mRNA splicing patterns.
  • Assessment of Androgen Receptor (AR) and AR-variant 7 (AR-v7) expression.
  • Evaluation of CRPC cell sensitivity to androgen deprivation.

Main Results:

  • Short-term CDK9 inhibition globally impairs mRNA splicing.
  • CDK9 inhibition leads to the loss of AR and AR-v7 expression due to splicing defects.
  • CDK9 expression is elevated in CRPC cells and patient samples.

Conclusions:

  • CDK9 inhibition compromises splicing in prostate cancer cells.
  • Targeting CDK9-mediated splicing defects can sensitize CRPC cells to androgen deprivation therapy by affecting androgen receptor expression.
Keywords:
Cyclin-dependent kinase 9bioinformaticso-glcnac transferaseprostate cancersplicing

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