Research Paper

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

Volume 12, Issue 10   November 15, 2011
Pages 908 - 914
http://dx.doi.org/10.4161/cbt.12.10.17681
Keywords: hypoxia, lung cancer, miR-155, microRNAs, radiosensitizer
Authors: Imran A. Babar, Jennifer Czochor, Allison Steinmetz, Joanne B. Weidhaas, Peter M. Glazer and Frank J. Slack

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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.

Received: July 13, 2011; Accepted: August 9, 2011

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