Authors: Babar IA; Czochor J; Steinmetz A; Weidhaas JB; Glazer PM; Slack FJ
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.
Keywords: Cell Hypoxia; Cell Line, Tumor; Cell Survival/genetics/radiation effects; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism; Lung Neoplasms/*genetics/metabolism; MicroRNAs/*genetics/metabolism; RNA, Small Interfering/metabolism; Radiation Tolerance/*genetics|
Journal: Cancer biology & therapy Volume: 12 Issue: 10 Pages: 908-14 Date: Oct. 27, 2011 PMID: 22027557 |
Babar IA, Czochor J, Steinmetz A, Weidhaas JB, Glazer PM, Slack FJ (2011) Inhibition of hypoxia-induced miR-155 radiosensitizes hypoxic lung cancer cells. Cancer biology & therapy 12: 908-14.
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