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Updated: Feb 24, 2026

miRNA Expression Analyses in Prostate Cancer Clinical Tissues
11:29

miRNA Expression Analyses in Prostate Cancer Clinical Tissues

Published on: September 8, 2015

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A comprehensive analysis of coregulator recruitment, androgen receptor function and gene expression in prostate

Song Liu1, Sangeeta Kumari2, Qiang Hu1

  • 1Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, United States.

Elife
|August 23, 2017
PubMed

Insights

Prostate cancer (CaP) relies on androgen receptor (AR) despite standard treatment. This study reveals how coregulators selectively control AR action, offering new therapeutic targets for CaP progression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Standard treatment for metastatic prostate cancer (CaP) targets androgen receptor (AR) signaling.
  • Despite initial treatment success, CaP often progresses due to continued AR reliance.
  • The precise molecular mechanisms regulating AR's transcriptional output in CaP remain incompletely understood.

Purpose of the Study:

  • To investigate how different coregulators selectively modulate androgen receptor (AR) transcriptional activity.
  • To identify novel therapeutic strategies by targeting AR's dependence on specific coregulators.

Main Methods:

  • Analysis of a 452-gene panel to assess AR target gene regulation by 18 distinct coregulators.
  • Gene-specific evaluation of coregulator function as coactivators or corepressors.
  • Investigation of AR binding site composition and its correlation with coregulator action and CaP progression.

Main Results:

  • Each of the 18 coregulators demonstrated selective control over AR-mediated gene expression, affecting 0-57% of the tested genes.
  • Coregulator-dependent AR action was linked to specific AR binding site characteristics and involvement in CaP biology.
  • A novel mechanism was identified where WDR77 integrates AR and p53 functions to regulate cell cycle progression in lethal CaP.

Conclusions:

  • Androgen receptor (AR) action is differentially controlled by various coregulators in a gene-specific manner.
  • Targeting the selective interactions between AR and its coregulators presents a promising therapeutic avenue for advanced prostate cancer.
  • The discovery of WDR77's role in coordinating AR and p53 offers a proof-of-principle for developing treatments that interfere with AR signaling pathways.
Keywords:
androgen deprivation therapycancer biologycastrationcastration-resistantcoactivatorcorepressorhumantranscription

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