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Updated: Jul 12, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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Cyclosporin A inhibits prostate cancer growth through suppression of E2F8 transcription factor in a MELK‑dependent

Da Young Lee1, Sanghoon Lee1, Young Sik Kim1

  • 1Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.

Oncology Reports
|October 27, 2023
PubMed

Insights

Cyclosporin A (CsA) shows promise for treating advanced prostate cancer by targeting the E2F8 gene. Inhibiting E2F8 and MELK may improve treatment outcomes and overcome resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Advanced prostate cancer treatment faces challenges due to limited effective options and therapeutic resistance.
  • Identifying novel druggable targets and strategies is crucial for improving patient outcomes.
  • Cyclosporin A (CsA) has demonstrated anticancer effects in prostate cancer models.

Purpose of the Study:

  • To investigate the role of E2F8 as a master transcription factor in prostate cancer.
  • To identify upstream regulators of E2F8, such as MELK.
  • To evaluate the therapeutic potential of targeting E2F8 and its regulators in prostate cancer.

Main Methods:

  • Analysis of CsA-specific gene signatures.
  • Identification of E2F8 as a key regulator.
  • Transcriptional regulatory network and Bayesian network analyses to identify MELK.
  • Experimental validation through gene knockdown in prostate cancer cell lines.

Main Results:

  • E2F8 expression increases with prostate cancer progression and correlates with poor prognosis.
  • MELK is identified as a crucial upstream regulator of E2F8.
  • Knockdown of E2F8 or MELK inhibits prostate cancer cell growth and colony formation.
  • High E2F8 and androgen receptor (AR) expression is linked to worse prognosis.
  • E2F8 inhibition enhances response to AR blockade therapy.

Conclusions:

  • Cyclosporin A (CsA) holds potential as an effective treatment for prostate cancer.
  • E2F8 plays an oncogenic role and is associated with clinical outcomes in prostate cancer.
  • Targeting E2F8 and MELK offers therapeutic and diagnostic insights for prostate cancer management.
Keywords:
E2F8cyclosporin Aoncogeneprognosisprostate cancer

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