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Dysregulation of spliceosome gene expression in advanced prostate cancer by RNA-binding protein PSF

Ken-Ichi Takayama1, Takashi Suzuki2, Tetsuya Fujimura3

  • 1Department of Functional Biogerontology, Tokyo Metropolitan Institute of Gerontology, Tokyo 173-0015, Japan.

Proceedings of the National Academy of Sciences of the United States of America
|September 13, 2017
PubMed

Insights

Researchers discovered that the RNA-binding protein PSF enhances androgen receptor (AR) expression in hormone-refractory prostate cancer by inducing spliceosome genes. Targeting PSF offers a potential therapeutic strategy for this aggressive cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Hormone-refractory prostate cancer (HRPC) progression is driven by androgen receptor (AR) signaling.
  • The precise mechanisms increasing AR signaling in HRPC remain incompletely understood.
  • Developing novel therapeutic strategies for HRPC is a critical unmet need.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying enhanced AR expression in HRPC.
  • To identify key regulators of AR splicing and expression in prostate cancer.
  • To explore potential therapeutic targets for HRPC.

Main Methods:

  • High-speed sequencing to identify global PSF-binding transcripts.
  • Analysis of spliceosome gene induction and AR expression.
  • Investigation of PSF's role in stabilizing noncoding RNAs and regulating gene expression in prostate cancer cells.
  • Assessment of PSF-mediated spliceosome complex formation.

Main Results:

  • Aberrant induction of spliceosome genes by RNA-binding protein PSF enhances AR splicing and expression in HRPC.
  • PSF stabilizes key long noncoding RNAs and AR-regulated gene expression.
  • Spliceosome-related gene mRNAs are primary targets of PSF, with their expression upregulated in HRPC.
  • PSF forms complexes with spliceosome proteins to promote AR splicing and expression.

Conclusions:

  • PSF plays a crucial role in driving AR signaling in hormone-refractory prostate cancer.
  • Targeting PSF and its associated pathways presents a promising therapeutic avenue for HRPC.
  • Understanding the PSF-spliceosome-AR axis is key to developing new treatments for advanced prostate cancer.
Keywords:
NONOPSFRNA-binding proteinandrogen receptorprostate cancer

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