Related Experiment Video

Updated: Dec 23, 2025

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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Loss of a Negative Feedback Loop between IRF8 and AR Promotes Prostate Cancer Growth and Enzalutamide Resistance

Hongxi Wu1, Linjun You1, Yan Li1

  • 1State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.

Cancer Research
|April 29, 2020
PubMed

Insights

Interferon regulatory factor 8 (IRF8) acts as a tumor suppressor in prostate cancer. Decreased IRF8 expression drives enzalutamide resistance by increasing androgen receptor (AR) levels, suggesting IRF8 as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Castration-resistant prostate cancer (CRPC) often develops resistance to enzalutamide, a novel androgen receptor (AR) antagonist, primarily due to AR overexpression.
  • Interferon regulatory factor 8 (IRF8) expression is altered in prostate cancer, decreasing in CRPC compared to normal tissue.

Purpose of the Study:

  • To investigate the role of IRF8 in prostate cancer progression and resistance to enzalutamide.
  • To elucidate the mechanism by which IRF8 influences AR levels and impacts treatment efficacy.

Main Methods:

  • Analysis of IRF8 expression in primary and castration-resistant prostate cancer (CRPC) tissues.
  • Investigation of the interaction between IRF8 and AR, including AR degradation pathways.
  • In vitro and in vivo studies assessing the impact of IRF8 knockdown on enzalutamide resistance.
  • Evaluation of interferon-alpha (IFNα) effects on IRF8 expression and enzalutamide efficacy.

Main Results:

  • Decreased IRF8 expression in CRPC correlates with disease progression and resistance to enzalutamide.
  • IRF8 interacts with AR and promotes its degradation via the ubiquitin/proteasome system.
  • Epigenetic silencing of IRF8 enhances AR-mediated prostate cancer progression and enzalutamide resistance.
  • IFNα treatment increases IRF8 expression, thereby overcoming enzalutamide resistance by targeting the IRF8-AR axis.

Conclusions:

  • IRF8 functions as a tumor suppressor in prostate cancer pathogenesis.
  • Targeting the IRF8-AR axis with agents like IFNα presents a potential therapeutic strategy to overcome enzalutamide resistance in CRPC.
  • IRF8-mediated AR degradation is a key mechanism underlying resistance to AR-targeted therapies.

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