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NR4A3 Suppresses Lymphomagenesis through Induction of Proapoptotic Genes

Alexander J A Deutsch1, Beate Rinner2, Martin Pichler3

  • 1Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. alexander.deutsch@medunigraz.at.

Cancer Research
|March 3, 2017
PubMed

Insights

Nuclear orphan receptor NR4A3 acts as a tumor suppressor in aggressive lymphomas, similar to NR4A1. Its low expression correlates with poor survival, while its activation induces lymphoma cell apoptosis and inhibits tumor growth.

Area of Science:

  • Molecular biology
  • Cancer research
  • Immunology

Background:

  • Nuclear orphan receptors, including NR4A1, play roles in cancer.
  • The function of NR4A3 in lymphomagenesis is not well understood.

Purpose of the Study:

  • To investigate the role of NR4A3 in aggressive lymphomas.
  • To compare the tumor suppressor functions of NR4A3 and NR4A1.

Main Methods:

  • Analyzing NR4A3 expression in lymphoma patients.
  • Overexpressing or pharmacologically activating NR4A3 in lymphoma cell lines.
  • Utilizing a mouse xenograft model of lymphoma.
  • Performing transcript analysis to identify apoptosis-related genes.

Main Results:

  • Low NR4A3 expression in aggressive lymphoma patients is linked to poor survival.
  • NR4A3 activation in lymphoma cell lines significantly increased apoptosis.
  • NR4A3 expression abrogated tumor growth in a mouse xenograft model.
  • NR4A3 and NR4A1 similarly induced apoptosis by upregulating pro-apoptotic genes like BAK, Puma, BIK, BIM, BID, and Trail.

Conclusions:

  • NR4A3 exhibits significant tumor suppressor functions in aggressive lymphomas.
  • NR4A3's impact on tumor suppression is comparable to that of NR4A1.
  • NR4A3 is a potential therapeutic target for aggressive lymphomas.

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