MYC drives aggressive prostate cancer by disrupting transcriptional pause release at androgen receptor targets. Academic Article uri icon

Overview

abstract

  • c-MYC (MYC) is a major driver of prostate cancer tumorigenesis and progression. Although MYC is overexpressed in both early and metastatic disease and associated with poor survival, its impact on prostate transcriptional reprogramming remains elusive. We demonstrate that MYC overexpression significantly diminishes the androgen receptor (AR) transcriptional program (the set of genes directly targeted by the AR protein) in luminal prostate cells without altering AR expression. Analyses of clinical specimens reveal that concurrent low AR and high MYC transcriptional programs accelerate prostate cancer progression toward a metastatic, castration-resistant disease. Data integration of single-cell transcriptomics together with ChIP-seq uncover an increase in RNA polymerase II (Pol II) promoter-proximal pausing at AR-dependent genes following MYC overexpression without an accompanying deactivation of AR-bound enhancers. Altogether, our findings suggest that MYC overexpression antagonizes the canonical AR transcriptional program and contributes to prostate tumor initiation and progression by disrupting transcriptional pause release at AR-regulated genes.

authors

publication date

  • May 13, 2022

Research

keywords

  • Prostatic Neoplasms
  • Receptors, Androgen

Identity

PubMed Central ID

  • PMC9106722

Scopus Document Identifier

  • 85130021714

Digital Object Identifier (DOI)

  • 10.1016/j.ygeno.2012.08.003

PubMed ID

  • 35562350

Additional Document Info

volume

  • 13

issue

  • 1