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A nucleotide regulates NR4A1 status in gastric cancer

Qi-Xiang Ma1, Miao Yin1, Qun-Ying Lei2

  • 1Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences & School of Basic Medical Sciences; Cancer Institutes, Key Laboratory of Breast Cancer in Shanghai; Shanghai Key Laboratory of Radiation Oncology; The Shanghai Key Laboratory of Medical Epigenetics, National Key Laboratory of Brain Function and Diseases, Shanghai Medical College, Fudan University, Shanghai, China.

Molecular Cell
|December 5, 2025
PubMed

Insights

Pyrimidine metabolite uridine monophosphate (UMP) regulates the nuclear receptor 4A1 (NR4A1). UMP binding prevents NR4A1 from suppressing gastric cancer, revealing a new therapeutic target.

Area of Science:

  • Molecular biology
  • Cancer research
  • Nuclear receptor signaling

Background:

  • The dual role of orphan nuclear receptor 4A1 (NR4A1) as both an oncogene and tumor suppressor is not fully understood.
  • Understanding the regulation of NR4A1 is crucial for developing targeted cancer therapies.

Purpose of the Study:

  • To investigate the endogenous regulatory mechanisms of NR4A1.
  • To elucidate how NR4A1's tumor-suppressive function is modulated in gastric cancer.

Main Methods:

  • Biochemical assays to confirm direct binding of UMP to NR4A1.
  • Cellular experiments to assess the impact of UMP on NR4A1 activity and gastric cancer cell proliferation.
  • Analysis of NR4A1 expression and UMP levels in gastric cancer tissues.

Main Results:

  • Uridine monophosphate (UMP), a pyrimidine metabolite, directly binds to NR4A1.
  • UMP binding abrogates the suppressive effect of NR4A1 on gastric cancer development.
  • This interaction reveals a novel mechanism controlling NR4A1's function in cancer.

Conclusions:

  • UMP acts as a key endogenous regulator of NR4A1, shifting its role in gastric cancer.
  • Targeting the NR4A1-UMP interaction could offer a new therapeutic strategy for gastric cancer.
  • Further research into metabolite-mediated regulation of nuclear receptors is warranted.

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