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Downregulation of ECRG4 by DNMT1 promotes EC growth via IRF3/IFN-γ/miR-29b/DNMT1/ECRG4 positive feedback loop

Ke Yang1, Shuaining Chai2, Helong Song2

  • 1Department of Oncology, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, 450003 Henan, China.

Iscience
|January 21, 2025
PubMed

Insights

Esophageal carcinoma (EC) shows reduced ECRG4 expression. ECRG4 activation of the IRF3/IFN-γ pathway, leading to miR-29b and reduced DNMT1, offers a potential therapeutic target for EC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Esophageal carcinoma (EC) is a prevalent global malignancy.
  • ECRG4 is frequently downregulated in EC, but its regulatory mechanisms are unclear.

Purpose of the Study:

  • To investigate the role and mechanism of ECRG4 in esophageal carcinoma.
  • To identify potential therapeutic targets for EC.

Main Methods:

  • Analysis of ECRG4 expression in EC tissues and cell lines.
  • Assessment of ECRG4's effect on cell proliferation in vitro and in vivo.
  • Elucidation of the molecular pathway involving ECRG4, IRF3, IFN-γ, miR-29b, and DNMT1.

Main Results:

  • ECRG4 expression is significantly downregulated in EC.
  • ECRG4 overexpression inhibits EC cell proliferation.
  • ECRG4 activates the IRF3/IFN-γ pathway, which upregulates miR-29b, subsequently reducing DNMT1 expression.
  • A positive feedback loop involving ECRG4, IRF3, IFN-γ, miR-29b, and DNMT1 was identified.

Conclusions:

  • ECRG4 plays a tumor-suppressive role in esophageal carcinoma.
  • The ECRG4/IRF3/IFN-γ/miR-29b/DNMT1 feedback loop is a key mechanism in EC.
  • This pathway represents a promising therapeutic target for esophageal carcinoma treatment.
Keywords:
CancerEpigeneticsMolecular mechanism of gene regulation

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