LIN28B 通过对 KRAS 的转录后控制赋予了放射抗性。
LIN28B confers radio-resistance through the posttranscriptional control of KRAS.
机构信息
Department of Biomedical Sciences, Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799, Korea.
出版信息
Exp Mol Med. 2009 Dec 31;41(12):912-8. doi: 10.3858/emm.2009.41.12.097.
To screen the differentially expressed microRNAs related to radio-resistance, we compared the microRNA profiles of lung cancer cells with different responses to ionizing radiation (IR). Of 328 microRNAs in microarray, 27 microRNAs were differentially expressed in NCI-H460 (H460) and NCI-H1299 (H1299) cells. Among them, let-7g was down-regulated in radio-resistant H1299 cells, and the level of let-7g was higher in radio-sensitive cells like Caski, H460, and ME180 in qRT-PCR analysis than in radio-resistant cells like A549, H1299, DLD1, and HeLa. Over-expression of let-7g in H1299 cells could suppress the translation of KRAS, and increase the sensitivity to IR. When we knockdown the expression of LIN28B, an upstream regulator of let-7g, the level of mature let-7g was increased in H1299 cells and the sensitivity to IR was also enhanced in LIN28B knockdown cells. From these data, we suggest that LIN28B plays an important role in radiation responses of lung cancer cells through inhibiting let-7g processing and increasing translation of KRAS.
为了筛选与放射抗性相关的差异表达 microRNA，我们比较了对电离辐射（IR）具有不同反应的肺癌细胞的 microRNA 谱。在微阵列中的 328 个 microRNAs 中，27 个 microRNAs 在 NCI-H460（H460）和 NCI-H1299（H1299）细胞中表达差异。其中，let-7g 在放射抗性 H1299 细胞中下调，而在像 Caski、H460 和 ME180 这样的放射敏感细胞中的水平比像 A549、H1299、DLD1 和 HeLa 这样的放射抗性细胞中的水平更高。在 H1299 细胞中过表达 let-7g 可以抑制 KRAS 的翻译，并增加对 IR 的敏感性。当我们敲低 let-7g 的上游调节因子 LIN28B 的表达时，H1299 细胞中成熟 let-7g 的水平增加，并且 LIN28B 敲低细胞对 IR 的敏感性也增强。从这些数据中，我们认为 LIN28B 通过抑制 let-7g 的加工和增加 KRAS 的翻译在肺癌细胞的放射反应中发挥重要作用。
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