Inhibition of hypoxia-induced miR-155 radiosensitizes hypoxic lung cancer cells
Inhibition of hypoxia-induced miR-155 radiosensitizes hypoxic lung cancer cells
复制标题
DOI：
10.4161/cbt.12.10.17681
复制
发表时间：
2011-11-15
影响因子：
3.6
通讯作者：
Slack, Frank J.
中科院分区：
文献类型：
--
作者：
Babar, Imran A.;Czochor, Jennifer;Slack, Frank J.
miR-155是一种重要的微小RNA（miRNA），可调节参与免疫和癌症相关途径的基因。miR-155在肺癌中过表达，这与患者预后不良相关。目前还不清楚miR-155在肺癌中是如何增加的，以及这种增加如何导致患者生存率降低。在这里，我们发现低氧条件诱导肺癌细胞中miR-155的表达，并引发验证靶点FOXO 3A的相应减少。此外，我们发现miR-155水平的增加对肺癌细胞具有放射保护作用，而miR-155的抑制使这些细胞放射增敏。此外，我们通过证明抗miR-155分子也使低氧肺癌细胞对辐射敏感，揭示了miR-155表达、低氧和辐射之间的治疗重要联系。我们的研究有助于解释miR-155如何在含有广泛缺氧微环境的肺癌中升高，并证明miR-155的抑制可能具有重要的治疗潜力，作为一种使缺氧肺癌细胞放射增敏的手段。
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.