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Updated: Jan 26, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

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Splicing Factors Have an Essential Role in Prostate Cancer Progression and Androgen Receptor Signaling

Ken-Ichi Takayama1,2

  • 1Department of Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan. ktakayama-tky@umin.ac.jp.

Biomolecules
|April 4, 2019
PubMed

Insights

Splicing factors are key drivers in prostate cancer progression, promoting androgen receptor (AR) expression and variants like AR-V7. Targeting these splicing factors offers a promising therapeutic strategy for castration-resistant prostate cancer (CRPC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Prostate cancer growth is initially controlled by the androgen-androgen receptor (AR) axis.
  • Most prostate cancers eventually develop resistance to castration, becoming castration-resistant prostate cancers (CRPCs).
  • Increased AR expression and its variants, such as AR-V7, are crucial for CRPC progression.

Purpose of the Study:

  • To explore the molecular mechanisms behind increased AR expression and AR-V7 generation in CRPC.
  • To highlight the role of RNA splicing factors in prostate cancer progression and AR signaling.
  • To identify splicing factors as potential therapeutic targets for CRPC.

Main Methods:

  • Review of recent literature on RNA splicing factors and their impact on AR signaling.
  • Analysis of aberrant regulation of splicing components in CRPC tissues.
  • Investigation of the role of RNA-binding protein splicing factor proline- and glutamine-rich (PSF/SFPQ) in AR variant production.
  • Evaluation of in vivo tumor growth inhibition by targeting splicing factors.
  • Correlation analysis between splicing factor expression and biochemical recurrence in prostate cancer patients.

Main Results:

  • RNA splicing factors significantly influence AR expression and the production of AR variants like AR-V7.
  • Aberrant regulation of splicing components is observed in CRPC tissues.
  • The splicing factor PSF/SFPQ enhances spliceosome gene expression, altering AR transcript variants.
  • Inhibition of specific splicing factors demonstrated tumor growth repression in vivo.
  • Altered splicing factor expression correlates with biochemical recurrence in prostate cancer patients.

Conclusions:

  • Splicing factors play a critical role in the progression of prostate cancer, particularly in the development of CRPC.
  • Targeting aberrant RNA splicing represents a novel and promising therapeutic strategy for prostate cancer.
  • Splicing factors are potential therapeutic targets for managing advanced prostate cancer and overcoming castration resistance.
Keywords:
NONOPSFandrogen receptorprostate cancersplicing factor

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