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MicroRNA Detection in Prostate Tumors by Quantitative Real-time PCR qPCR
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BAZ2A-RNA mediated association with TOP2A and KDM1A represses genes implicated in prostate cancer

Marcin Roganowicz1,2, Dominik Bär1, Cristiana Bersaglieri1

  • 1Department of Molecular Mechanisms of Disease, DMMD, University of Zurich, Zurich, Switzerland.

Life Science Alliance
|May 15, 2023
PubMed

Insights

BAZ2A protein represses genes in prostate cancer via an RNA-binding mechanism involving TOP2A and KDM1A. This novel pathway offers potential for stratifying prostate cancer risk and guiding treatment strategies.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • BAZ2A protein typically represses ribosomal RNA genes (rDNA).
  • In prostate cancer (PCa), BAZ2A represses additional genes linked to metastatic disease.
  • The precise mechanisms of BAZ2A-mediated repression in PCa are not fully understood.

Purpose of the Study:

  • To elucidate the novel mechanisms of BAZ2A-mediated gene repression in prostate cancer.
  • To investigate the role of the BAZ2A TAM domain in PCa gene regulation.
  • To identify potential therapeutic targets and biomarkers for prostate cancer.

Main Methods:

  • Investigated BAZ2A's interaction with target genes and regulatory proteins using its RNA-binding TAM domain.
  • Examined the association of BAZ2A with topoisomerase 2A (TOP2A) and KDM1A in PCa cells.
  • Utilized pharmacological inhibition of TOP2A and KDM1A to assess their impact on BAZ2A-repressed genes.

Main Results:

  • BAZ2A utilizes its TAM domain and associated RNA to interact with TOP2A and KDM1A in PCa.
  • TOP2A and KDM1A expression positively correlates with BAZ2A levels in both localized and metastatic PCa.
  • Inhibition of TOP2A and KDM1A reactivates BAZ2A-repressed genes regulated by inactive enhancers, distinct from rDNA regulation.

Conclusions:

  • Discovered a novel, RNA-based mechanism of gene regulation by BAZ2A in prostate cancer.
  • RNA-mediated interactions involving BAZ2A, TOP2A, and KDM1A repress critical PCa genes.
  • These findings suggest BAZ2A-TOP2A-KDM1A interactions could be valuable for prostate cancer risk stratification and treatment.

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