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

Tzu Ting Huang, Yueh Hsin Ping, An Ming Wang, Chia Chi Ke, Wen Liang Fang, Kuo Hung Huang, Hsin Chen Lee, Chin Wen Chi, Tian-Shun Tsai

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Gastric carcinoma is one of the most common malignancies and the third highest cause of global cancer-related death. Notch2 receptor intracellular domain (N2IC), the activated form of Notch2 receptor, enhances gastric carcinogenesis. MicroRNAs (miRNAs) act as either oncogenes or tumor suppressors in tumorigenesis and cross-talk with Notch pathways. Herein, microRNA-23b (miR-23b) was identified as a Notch2 receptor-related miRNA and its role in gastric carcinogenesis was investigated. Levels of miR-23b in stomach adenocarcinoma samples were down-regulated, whereas those of Notch2 receptor, v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets1), and E2F1 transcripts were up-regulated. Results also showed that N2IC down-regulated miR-23b expression in gastric cancer cells through up-regulating E2F1. The miR-23b inhibited gastric tumorigenesis including growth, viability, epithelial-mesenchymal transition, and abilities of colony formation, migration, invasion, and tumorsphere formation. Mechanistically, miR-23b suppressed tumor progression and pluripotency gene expression and affected tumorsphere ultra-structure in gastric cancer cells via targeting Notch2 receptor or Ets1. Furthermore, miR-23b diminished the xenografted tumor growth and lung metastasis of SC-M1 gastric cancer cells through Notch2 pathway. Our results suggest that Notch2 pathway and miR-23b interplay in a reciprocal regulation loop in gastric cancer cells and this axis plays an important role in gastric carcinogenesis.

Original languageEnglish
Pages (from-to)18012-18026
Number of pages15
JournalOncotarget
Volume6
Issue number20
Publication statusPublished - 2015

Keywords

  • E2F1
  • Ets1
  • Gastric carcinogenesis
  • miR-23b
  • Notch2 receptor

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Huang, T. T., Ping, Y. H., Wang, A. M., Ke, C. C., Fang, W. L., Huang, K. H., Lee, H. C., Chi, C. W., & Tsai, T-S. (2015). The reciprocal regulation loop of Notch2 pathway and miR-23b in controlling gastric carcinogenesis. Oncotarget, 6(20), 18012-18026.