MiR‐182 enhances radioresistance in non‐small cell lung cancer cells by regulating <scp>FOXO</scp>3

Abstract

Upregulated in lung cancer, miRNA-182 was found to be related to cancer proliferation and chemoresistance. However, there is no report on the role of miR-182 in radioresistance, which is a main obstacle of radiotherapy. In this study, we aim to depict the effect of miR-182 inhibition on cellular sensitivity to ionizing radiation. Our data confirm that miR-182 is upregulated in lung cancers and tissues and that miR-182 is responsive to irradiation. We also show that miR-182 knockdown suppresses cell proliferation and increases cell apoptosis after irradiation. DNA damage remains unrepaired in miR-182 knockdown cells, which results in cell cycle arrest. Finally, we find that FOXO3 is a direct target of miR-182 and that overexpression of FOXO3 enhances radiation resistance in miR-182 knockdown cells. In conclusion, our data suggest that miR-182 might account for radioresistance in lung cancer and that miR-182-FOXO3 provides a novel radiosensitizing target.