Inhibition of hypoxia-induced miR-155 radiosensitizes hypoxic lung cancer cells

Cancer Biol Ther. 2011 Nov 15;12(10):908-14. doi: 10.4161/cbt.12.10.17681. Epub 2011 Nov 15.

Abstract

miR-155 is a prominent microRNA (miRNA) that regulates genes involved in immunity and cancer-related pathways. miR-155 is overexpressed in lung cancer, which correlates with poor patient prognosis. It is unclear how miR-155 becomes increased in lung cancers and how this increase contributes to reduced patient survival. Here, we show that hypoxic conditions induce miR-155 expression in lung cancer cells and trigger a corresponding decrease in a validated target, FOXO3A. Furthermore, we find that increased levels of miR-155 radioprotects lung cancer cells, while inhibition of miR-155 radiosensitizes these cells. Moreover, we reveal a therapeutically important link between miR-155 expression, hypoxia, and irradiation by demonstrating that anti-miR-155 molecules also sensitize hypoxic lung cancer cells to irradiation. Our study helps explain how miR-155 becomes elevated in lung cancers, which contain extensive hypoxic microenvironments, and demonstrates that inhibition of miR-155 may have important therapeutic potential as a means to radiosensitize hypoxic lung cancer cells.

Publication types

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

MeSH terms

  • Cell Hypoxia
  • Cell Line, Tumor
  • Cell Survival / genetics
  • Cell Survival / radiation effects
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • RNA, Small Interfering / metabolism
  • Radiation Tolerance / genetics*

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN155 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering