Laboratory of Molecular and Genomic Medicine, Department of Biomedical Sciences, Seoul National University College of Medicine, Korea.
Exp Mol Med. 2011 May 31;43(5):298-304. doi: 10.3858/emm.2011.43.5.031.
The activation of nuclear factor-kappa B1 (NFkB1) in cancer cells may confer resistance to ionizing radiation (IR). To enhance the therapeutic efficiency of IR in lung cancer, we screened for microRNAs (miRNAs) that suppress NFkB1 and observed their effects on radiosensitivity in a human lung cancer cell line. From time series data of miRNA expression in γ-irradiated H1299 human lung cancer cells, we found that the expression of miR-9 was inversely correlated with that of NFκB1. Overexpression of miR-9 down-regulated the level of NFκB1 in H1299 cells, and the surviving fraction of γ-irradiated cells was decreased. Interestingly, let-7g also suppressed the expression of NFκB1, although there was no canonical target site for let-7g in the NFκB1 3' untranslated region. From these results, we conclude that the expression of miR-9 and let-7g could enhance the efficiency of radiotherapy for lung cancer treatment through the inhibition of NFκB1.
肿瘤细胞中核因子-κB1（NFkB1）的激活可能导致其对电离辐射（IR）产生抗性。为了提高肺癌中 IR 的治疗效率，我们筛选了抑制 NFkB1 的 microRNAs（miRNAs），并观察它们在人肺癌细胞系中对放射敏感性的影响。从γ-辐射的 H1299 人肺癌细胞中 miRNA 表达的时间序列数据中，我们发现 miR-9 的表达与 NFκB1 的表达呈负相关。miR-9 的过表达下调了 H1299 细胞中 NFκB1 的水平，并且γ-照射细胞的存活分数降低。有趣的是，let-7g 也抑制了 NFκB1 的表达，尽管在 NFκB1 的 3'非翻译区没有 let-7g 的典型靶位。根据这些结果，我们得出结论，miR-9 和 let-7g 的表达可以通过抑制 NFκB1 来提高肺癌治疗的放射治疗效率。
