Related Experiment Video

Updated: Feb 22, 2026

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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Targeting a Single Alternative Polyadenylation Site Coordinately Blocks Expression of Androgen Receptor mRNA Splice

Jamie L Van Etten1, Michael Nyquist1,2, Yingming Li3

  • 1Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.

Cancer Research
|September 21, 2017
PubMed

Insights

Researchers identified a key signal in prostate cancer that controls androgen receptor (AR) variants. Blocking this signal inhibits AR variant expression and CRPC cell growth, offering a new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer progression to castration-resistant prostate cancer (CRPC) is a major cause of cancer death in men.
  • Androgen receptor (AR) splice variants, such as AR-V7, drive CRPC by promoting resistance to AR-targeted therapies.
  • Currently, no treatments specifically target AR variants in CRPC.

Purpose of the Study:

  • To investigate the regulatory mechanism controlling AR splice variant expression in CRPC.
  • To identify potential therapeutic targets for overcoming resistance to AR-targeted therapies in CRPC.

Main Methods:

  • Utilized morpholino technology to block a specific polyadenylation signal in AR intron 3.
  • Employed gene silencing techniques to target the polyadenylation factor CPSF1.
  • Assessed the impact of these interventions on AR variant splicing and CRPC cell growth.

Main Results:

  • A single polyadenylation signal in AR intron 3 was found to coordinately regulate the splicing of multiple AR variants (AR-V7, AR-V1, AR-V9).
  • Blocking this signal or silencing CPSF1 induced a splice switch, inhibiting AR variant expression.
  • This inhibition effectively blocked androgen-independent growth of CRPC cells.

Conclusions:

  • The polyadenylation signal in AR intron 3 is a critical regulator of AR variant expression in CRPC.
  • Targeting this polyadenylation signal represents a promising therapeutic strategy to inhibit a broad spectrum of AR variants.
  • This approach could lead to novel treatments for castration-resistant prostate cancer.

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