Department of Respiratory Medicine, People's Hospital of Haining, Haining, China.
Clin Exp Pharmacol Physiol. 2019 Feb;46(2):137-143. doi: 10.1111/1440-1681.13041.
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.
在肺癌中上调的 microRNA-182 被发现与癌症增殖和化疗耐药有关。然而，miR-182 在放射抵抗中的作用尚未见报道，而放射抵抗是放射治疗的主要障碍。在本研究中，我们旨在描述抑制 miR-182 对细胞对电离辐射敏感性的影响。我们的数据证实，miR-182 在肺癌和组织中上调，并且 miR-182 对辐射有反应。我们还表明，miR-182 敲低可抑制照射后的细胞增殖并增加细胞凋亡。miR-182 敲低细胞中的 DNA 损伤仍未修复，导致细胞周期停滞。最后，我们发现 FOXO3 是 miR-182 的直接靶标，并且 FOXO3 的过表达增强了 miR-182 敲低细胞的辐射抗性。总之，我们的数据表明，miR-182 可能导致肺癌中的放射抵抗，并且 miR-182-FOXO3 提供了一种新的放射增敏靶标。
