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Histone Demethylase LSD1 Regulates Kidney Cancer Progression by Modulating Androgen Receptor Activity

Kyoung-Hwa Lee1, Byung-Chan Kim1, Seung-Hwan Jeong2

  • 1Department of Urology, Seoul National University Hospital, Seoul 03080, Korea.

International Journal of Molecular Sciences
|August 28, 2020
PubMed

Insights

Lysine-specific histone demethylase 1 (LSD1) regulates kidney cancer growth by controlling androgen receptor (AR) activity. Inhibiting LSD1 may offer a new therapeutic strategy for kidney cancer treatment.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Kidney cancer presents significant treatment challenges with current therapies.
  • Identifying novel therapeutic targets is crucial for developing effective kidney cancer drugs.

Purpose of the Study:

  • To investigate the role of lysine-specific histone demethylase 1 (LSD1) in regulating androgen receptor (AR) activity in kidney cancer.
  • To evaluate the therapeutic potential of LSD1 inhibition in kidney cancer treatment.

Main Methods:

  • Knock-down of LSD1 in kidney cancer cell lines to assess effects on AR target gene expression and AR binding.
  • Treatment of kidney cancer cells with the LSD1 inhibitor pargyline and the AR inhibitor enzalutamide.
  • In vivo studies using a xenograft mouse model to evaluate the impact of LSD1 down-regulation on tumor growth.

Main Results:

  • LSD1 knockdown reduced AR target gene expression, AR binding to promoters, and altered histone methylation.
  • LSD1 inhibition with pargyline decreased kidney cancer cell growth, migration, and repressed epithelial-mesenchymal transition (EMT) markers.
  • Combined treatment with pargyline and enzalutamide showed additive effects, and LSD1 down-regulation attenuated tumor growth in vivo.

Conclusions:

  • LSD1 epigenetically regulates kidney cancer cell growth through AR transcription factors.
  • LSD1 inhibitors represent a promising therapeutic candidate for kidney cancer treatment.
Keywords:
LSD1androgen receptorenzalutamidehistone methylationkidney cancer

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