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Updated: Dec 14, 2025

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients

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BRD4 regulates key transcription factors that drive epithelial-mesenchymal transition in castration-resistant

Jordan S Shafran1,2, Naser Jafari1, Allison N Casey1,3

  • 1Boston University-Boston Medical Center Cancer Center, Boston, MA, 02118, USA.

Prostate Cancer and Prostatic Diseases
|July 22, 2020
PubMed
Abstract

Insights

BRD4 protein drives the epithelial-to-mesenchymal transition (EMT) in prostate cancer. Targeting BRD4 offers a new therapeutic strategy for metastatic castration-resistant prostate cancer (mCRPC) and emerging chemoresistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Androgen deprivation therapies (ADT) are effective but lead to chemoresistant prostate cancer.
  • Metastatic castration-resistant prostate cancer (mCRPC) progresses due to resistance mechanisms and epithelial-to-mesenchymal transition (EMT).
  • Understanding transcriptional networks driving mCRPC progression is crucial for developing new therapies.

Purpose of the Study:

  • To investigate the role of Bromodomain and ExtraTerminal (BET) family proteins in regulating EMT in prostate cancer.
  • To identify specific BET proteins that influence EMT and correlate their expression with patient survival outcomes.

Main Methods:

  • Systematic manipulation of BET proteins (BRD2, BRD3, BRD4) in prostate cancer cell lines.
  • Analysis of The Cancer Genome Atlas (TCGA) data to correlate BET gene expression with EMT markers and patient survival.
  • Treatment of cells with TGFß signaling and selective BRD4 protein degrader (MZ1).

Main Results:

  • BRD4, but not BRD2 or BRD3, regulates SNAI1 and SNAI2, key EMT transcription factors.
  • Downregulation of SNAI1/SNAI2 by BRD4 inhibition increases E-cadherin expression, reversing EMT.
  • BRD4 expression correlates with improved survival outcomes in prostate cancer patients.
  • Selective BRD4 degradation ablates TGFß-induced EMT.

Conclusions:

  • BRD4 is a key regulator of EMT in prostate cancer.
  • BRD4 represents a novel druggable target for treating mCRPC.
  • BRD4-selective protein degraders show promise for overcoming chemoresistance in advanced prostate cancer.

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