Related Experiment Video

Updated: Apr 11, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

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Nuclear Receptor 4A1 (NR4A1) as a Drug Target for Renal Cell Adenocarcinoma

Erik Hedrick1, Syng-Ook Lee2, Gyungeun Kim3

  • 1Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, United States of America.

Plos One
|June 3, 2015
PubMed

Insights

Targeting the NR4A1 receptor with novel C-DIM compounds inhibits renal cell carcinoma (RCC) growth and induces apoptosis. These NR4A1 antagonists offer a promising new chemotherapy strategy for RCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The orphan nuclear receptor NR4A1 plays a pro-oncogenic role in cancer.
  • NR4A1 influences cell survival and growth by activating mTOR signaling and regulating oxidative stress genes.

Purpose of the Study:

  • To investigate the therapeutic potential of NR4A1 antagonists in renal cell carcinoma (RCC).
  • To evaluate the efficacy of C-DIM compounds as NR4A1 antagonists in RCC models.

Main Methods:

  • NR4A1 knockdown using oligonucleotides in RCC cell lines (ACHN and 786-O).
  • Treatment of RCC cells and xenografts with specific C-DIM analogs (DIM-C-pPhOH and DIM-C-pPhCO2Me).
  • Assessment of cell proliferation, apoptosis, gene expression (bcl-2, survivin, EGFR, TXNDC5, IDH1), and signaling pathways (mTOR).

Main Results:

  • NR4A1 knockdown significantly reduced RCC cell proliferation and induced apoptosis.
  • NR4A1 knockdown decreased expression of pro-survival genes and inhibited mTOR signaling, while increasing stress.
  • DIM-C-DIM analogs demonstrated comparable anti-cancer effects to NR4A1 knockdown, inhibiting growth and inducing apoptosis in RCC cells.

Conclusions:

  • NR4A1 antagonists effectively target multiple pro-survival and growth pathways in RCC.
  • C-DIM compounds targeting NR4A1 represent a novel therapeutic strategy for RCC.
  • NR4A1 antagonists show potential for treating RCC and related tumors.

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