Related Experiment Video

Updated: Jun 27, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
10:51

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

Published on: November 15, 2013

MerTK Is Regulated by Orphan Nuclear Receptor 4A1 (NR4A1) and NR4A2 in Colon Cancer Cells

Gargi Sivaram1, Srijana Upadhyay2, Sarah Kakwan3

  • 1Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843, USA.

Cancers
|June 26, 2026
PubMed

Insights

DIM-3,5 compounds, dual NR4A1/NR4A2 ligands, inhibit MerTK expression in colon cancer cells by targeting NR4A/Sp complexes. This reveals a novel therapeutic strategy for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Orphan nuclear receptors NR4A1 and NR4A2 are overexpressed in solid tumors.
  • These receptors promote tumor growth and MerTK expression.

Purpose of the Study:

  • Investigate the effect of DIM-3,5 compounds on MerTK expression.
  • Elucidate the regulatory mechanism of MerTK in colon cancer cells.

Main Methods:

  • Utilized colon cancer cell lines (SW480, HCT116, CT26).
  • Administered DIM-3,5 compounds and performed gene knockdown (NR4A1, NR4A2, Sp1, Sp3, Sp4).
  • Employed chromatin immunoprecipitation and luciferase reporter assays.

Main Results:

  • DIM-3,5 compounds significantly downregulated MerTK protein and RNA expression.
  • NR4A1/NR4A2 knockdown decreased MerTK expression.
  • MerTK expression is regulated by NR4A/Sp complexes (NR4A1, NR4A2, Sp1, Sp3, Sp4).

Conclusions:

  • DIM-3,5 ligands act as novel inhibitors of MerTK expression in cancer cells.
  • NR4A1 and NR4A2 participate in MerTK regulation.
  • DIM-3,5 compounds represent a potential therapeutic strategy targeting MerTK in cancer.
Keywords:
DIM-3,5 ligandsMerTKNR4A1NR4A2colon cancertranscriptional regulation

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