MicroRNA-135b acts as a tumor promoter by targeting the hypoxia-inducible factor pathway in genetically defined mouse model of head and neck squamous cell carcinoma

Cancer Lett. 2013 May 1;331(2):230-8. doi: 10.1016/j.canlet.2013.01.003. Epub 2013 Jan 20.

Abstract

Here in, we investigated the mechanism underlying overexpression of miR-135b in the human head and neck squamous cell carcinoma (HNSCC) cell lines and in the HNSCC mouse model. Exogenous expression of miR-135b in these cell lines increased cell proliferation, migration, and colony formation. Gene silencing analysis revealed that miR-135b affects a regulator that inhibits hypoxia-inducible factor (HIF). Increased miR-135b expression was positively correlated with HIF-1α expression and microvessel density in the HNSCC model. Thus, our data demonstrate that miR-135b acts as a tumor promoter by promoting cancer cell proliferation, colony formation, survival, and angiogenesis through activation of HIF-1α in HNSCC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Proliferation
  • Cells, Cultured
  • Disease Models, Animal
  • Gene Deletion
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Hypoxia-Inducible Factor 1 / metabolism*
  • Mice
  • Mice, Knockout
  • MicroRNAs / physiology*
  • PTEN Phosphohydrolase / genetics
  • Protein Serine-Threonine Kinases / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / genetics

Substances

  • Hypoxia-Inducible Factor 1
  • MicroRNAs
  • Mirn135 microRNA, mouse
  • Receptors, Transforming Growth Factor beta
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I
  • PTEN Phosphohydrolase
  • Pten protein, mouse