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The reciprocal regulation loop of Notch2 pathway and miR-23b in controlling gastric carcinogenesis

Tzu-Ting Huang1,2, Yueh-Hsin Ping1, An-Ming Wang2

  • 1Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

Oncotarget
|June 5, 2015
PubMed

Insights

MicroRNA-23b (miR-23b) acts as a tumor suppressor in gastric cancer by inhibiting growth and metastasis. It reciprocally regulates the Notch2 pathway, offering a potential therapeutic target for this common malignancy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Gastric carcinoma is a leading cause of cancer death globally.
  • The Notch2 receptor intracellular domain (N2IC) promotes gastric carcinogenesis.
  • MicroRNAs (miRNAs) play crucial roles in tumorigenesis and interact with Notch signaling.

Purpose of the Study:

  • To investigate the role of microRNA-23b (miR-23b) in gastric carcinogenesis.
  • To elucidate the relationship between miR-23b and the Notch2 pathway in gastric cancer.

Main Methods:

  • Analysis of miR-23b, Notch2 receptor, Ets1, and E2F1 transcript levels in gastric adenocarcinoma samples.
  • Investigation of N2IC-mediated regulation of miR-23b expression in gastric cancer cells.
  • Assessment of miR-23b's effects on gastric cancer cell proliferation, migration, invasion, and tumorsphere formation.
  • Evaluation of miR-23b's impact on xenografted tumor growth and lung metastasis.

Main Results:

  • miR-23b was down-regulated in gastric adenocarcinoma, while Notch2 receptor, Ets1, and E2F1 were up-regulated.
  • N2IC suppressed miR-23b expression by up-regulating E2F1.
  • miR-23b inhibited gastric tumorigenesis, including growth, viability, epithelial-mesenchymal transition, and metastatic potential.
  • miR-23b targeted Notch2 receptor and Ets1, suppressing tumor progression and pluripotency gene expression.
  • miR-23b reduced tumor growth and lung metastasis in vivo via the Notch2 pathway.

Conclusions:

  • The Notch2 pathway and miR-23b exhibit reciprocal regulation in gastric cancer cells.
  • This miR-23b/Notch2 axis is critical for gastric carcinogenesis.
  • miR-23b functions as a tumor suppressor, highlighting its therapeutic potential.
Keywords:
E2F1Ets1Notch2 receptorgastric carcinogenesismiR-23b

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