Related Experiment Video

Updated: Jun 13, 2025

miRNA Expression Analyses in Prostate Cancer Clinical Tissues
11:29

miRNA Expression Analyses in Prostate Cancer Clinical Tissues

Published on: September 8, 2015

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OGDHL regulates tumor growth, neuroendocrine marker expression, and nucleotide abundance in prostate cancer

Matthew J Bernard1, Angel Ruiz1, Johnny A Diaz1

  • 1Molecular Biology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Biorxiv : the Preprint Server for Biology
|June 12, 2025
PubMed

Insights

Loss of Oxoglutarate Dehydrogenase-Like (OGDHL) impairs prostate cancer growth and alters treatment response by affecting nucleotide metabolism. This unexpected role highlights OGDHL as a potential therapeutic target in prostate cancer.

Area of Science:

  • Cancer Metabolism
  • Molecular Oncology
  • Prostate Cancer Research

Background:

  • Prostate cancer cells exhibit metabolic plasticity, enabling adaptation to therapies targeting androgen receptor (AR) signaling.
  • Nucleotide metabolism is crucial for treatment-resistant prostate cancer, supporting DNA replication, repair, and cell fate.
  • Targeting novel regulators of nucleotide metabolism could offer less toxic therapeutic strategies.

Purpose of the Study:

  • To identify novel regulators of nucleotide metabolism in treatment-resistant prostate cancer.
  • To investigate the role of Oxoglutarate Dehydrogenase-Like (OGDHL) in prostate cancer progression and therapeutic plasticity.
  • To explore OGDHL as a potential therapeutic target distinct from normal cellular functions.

Main Methods:

  • Identification of OGDHL as a regulator of nucleotide metabolism and tumor growth in prostate cancer.
  • Assessment of OGDHL's impact on cell proliferation, tumor formation, and TCA cycle activity.
  • Analysis of OGDHL's effect on DNA damage response (Ɣ2AX) and AR inhibition-induced plasticity (DLL3, HES6).

Main Results:

  • Loss of OGDHL impairs prostate cancer cell proliferation and tumor formation with minimal impact on TCA cycle.
  • OGDHL deficiency reduces nucleotide metabolite pools and induces DNA damage response.
  • OGDHL loss suppresses neuroendocrine differentiation markers (DLL3, HES6) under AR inhibition.
  • OGDHL is highly expressed in neuroendocrine prostate cancer (NEPC).

Conclusions:

  • OGDHL unexpectedly promotes prostate cancer progression by sustaining nucleotide pools for proliferation and DNA repair.
  • OGDHL plays a role in AR inhibition-induced plasticity, suggesting involvement in treatment resistance.
  • OGDHL represents a promising therapeutic target for prostate cancer, particularly NEPC.

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