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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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LSD1-Mediated Epigenetic Reprogramming Drives CENPE Expression and Prostate Cancer Progression

Yi Liang1, Musaddeque Ahmed1, Haiyang Guo1

  • 1Princess Margaret Cancer Centre/University Health Network, Toronto, Ontario, Canada.

Cancer Research
|September 17, 2017
PubMed

Insights

Chromatin modifier LSD1 reprogramming drives castration-resistant prostate cancer (CRPC) by activating cell-cycle genes like CENPE. Targeting CENPE significantly reduces tumor growth, offering a new therapeutic strategy for CRPC.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Androgen receptor (AR) signaling drives prostate cancer.
  • Androgen-deprivation therapy (ADT) is a standard treatment but leads to castration-resistant prostate cancer (CRPC).
  • The chromatin modifier LSD1 regulates AR activity.

Purpose of the Study:

  • Investigate epigenetic reprogramming of LSD1 in CRPC.
  • Identify genes regulated by LSD1 in CRPC.
  • Determine the therapeutic potential of targeting LSD1-regulated genes.

Main Methods:

  • Analysis of LSD1 epigenetic reprogramming in CRPC models.
  • Identification of LSD1 and AR co-binding targets.
  • Genetic deletion and pharmacological inhibition of CENPE.

Main Results:

  • LSD1 undergoes epigenetic reprogramming in CRPC.
  • Reprogramming activates cell-cycle genes, including CENPE, via LSD1 and AR co-binding.
  • Loss of RB1 is associated with CENPE regulation in CRPC.
  • CENPE inhibition significantly decreases CRPC tumor growth.

Conclusions:

  • LSD1-mediated epigenetic reprogramming drives CRPC progression.
  • CENPE is a key driver of CRPC growth.
  • Targeting CENPE offers a promising therapeutic strategy for CRPC.

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