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

Authors: Babar, Imran A; Czochor, Jennifer; Steinmetz, Allison; Weidhaas, Joanne B; Glazer, Peter M; Slack, Frank J

Published In Cancer Biol Ther, (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.

PubMed ID: 22027557

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*