miR-200b suppresses cell growth, migration and invasion by targeting Notch1 in nasopharyngeal carcinoma

Cell Physiol Biochem. 2013;32(5):1288-98. doi: 10.1159/000354527. Epub 2013 Nov 22.

Abstract

Background/aims: MicroRNAs (miRNAs) are a class of small noncoding RNA molecules that play important roles in carcinogenesis and tumor progression. We investigated the roles and mechanisms of miR-200b in human nasopharyngeal carcinoma (NPC).

Methods: We used quantitative real-time polymerase chain reaction (qRT-PCR) analyses to measure levels of miR-200b and Notch1 in NPC specimens and cell lines. Human NPC cell lines stably expressing miR-200b or control were used to analyze the tumour-suppressive effect of miR-200b. Luciferase reporter assays were used to determine the association between miR-200b and the Notch1 3' untranslated region.

Results: We found that miR-200b is significantly downregulated in NPC tissues and cell lines. Gain-of-function and loss-of-function studies demonstrated that miR-200b suppresses NPC cell growth, migration and invasion in vitro. Importantly, overexpression of miR-200b effectively repressed tumor growth in nude mouse models. Integrated analysis identified Notch1 as a direct and functional target of miR-200b. Overexpression of Notch1 reversed the inhibitory effect of miR-200b on NPC cell growth and invasion.

Conclusion: These results indicate that miR-200b exerts tumor-suppressive effects in NPC carcinogenesis through the suppression of Notch1 expression and suggest a therapeutic application of miR-200b in NPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Carcinoma
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / physiology*
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / pathology*
  • Receptor, Notch1 / genetics*

Substances

  • 3' Untranslated Regions
  • MIRN200 microRNA, human
  • MicroRNAs
  • NOTCH1 protein, human
  • Receptor, Notch1