MicroRNA-Mediated Processes are Essential for the Cellular Radiation Response
MicroRNA-Mediated Processes are Essential for the Cellular Radiation Response
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DOI：
10.1667/rr2638.1
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发表时间：
2011-11-01
影响因子：
3.4
通讯作者：
Moertl, Simone
中科院分区：
文献类型：
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作者：
Kraemer, Anne;Anastasov, Natasa;Moertl, Simone
Kraemer，A.，Anastasov，N.，Angermeier，M.，Winkler，K.，阿特金森，M。J.和Moertl，S. MicroRNA介导的过程对细胞辐射反应至关重要。Radiat. Res. 176，575-586（2011）.需要详细了解决定细胞对辐射的可变敏感性的机制，以改进放射疗法以及鉴定具有先天性辐射超敏性的个体。MicroRNA（miRNAs）是一类转录后调节蛋白质表达的非编码小RNA。已经显示了响应于电离辐射的miRNA表达模式的改变，但是几乎没有数据描述这些miRNA变化的功能影响。我们在这里报告的结果的功能性作用的miRNA的辐射反应在永生化和原代内皮细胞的研究。通过使用RNAi下调Argonaut e-2（AGO 2）或DICER蛋白实现了对miRNA表达的全面抑制。DICER或AGO 2的减少导致照射后细胞死亡增加，表明miRNA的促生存功能。此外，虽然细胞周期检查点激活和凋亡受到损害，但DNA双链断裂修复不受miRNAs缺乏的影响。这些途径的差异敏感性意味着两个响应途径的独立激活，而不是协同的DNA损伤响应。采用TaqMan低密度阵列技术鉴定2.5戈伊照射后发生变化的miRNAs。在辐射暴露后4小时或24小时显示上调的miRNAs中，我们能够建立三种miRNAs的促生存和抗凋亡功能。总之，我们的数据表明，在辐射反应过程中，miRNA介导的基因调控具有普遍的促生存作用。我们显示了辐射细胞中miRNA、凋亡和细胞周期检查点激活之间的功能关联。(C)2011年，辐射研究协会。
Kraemer, A., Anastasov, N., Angermeier, M., Winkler, K., Atkinson, M. J. and Moertl, S. MicroRNA-Mediated Processes are Essential for the Cellular Radiation Response. Radiat. Res. 176, 575-586 (2011).A detailed understanding of the mechanisms that determine the variable cellular sensitivity to radiation is needed for improved radiation therapy as well as for the identification of individuals with innate radiation hypersensitivity. MicroRNAs (miRNAs) are a class of small non-coding RNAs that post-transcriptionally regulate protein expression. Alterations in miRNA expression patterns in response to ionizing radiation have been shown, but there are almost no data describing the functional impact of these miRNA changes. We report here the results of studies on the functional roles of miRNAs in the radiation response in immortalized and primary endothelial cells. Global suppression of miRNA expression was achieved through downregulation of Argonaut e-2 (AGO2) or DICER proteins using RNAi. The reductions in either DICER or AGO2 led to increased cell death after irradiation, indicating a prosurvival function of miRNAs. Furthermore, while cell cycle checkpoint activation and apoptosis were compromised, DNA double-strand break repair was not affected by the lack of miRNAs. The differential sensitivity of these pathways implies the independent activation of the two response pathways rather than a concerted DNA damage response. The miRNAs that were changed after 2.5 Gy irradiation were identified by TaqMan-based low-density array technology. Of the miRNAs showing an upregulation 4 h or 24 h after radiation exposure, we were able to establish prosurvival and antiapoptotic functions for three miRNAs. Taken together, our data indicate a general prosurvival role for miRNA-mediated gene regulation during the radiation response. We show a functional association between miRNAs, apoptosis and cell cycle checkpoint activation in irradiated cells. (C) 2011 by Radiation Research Society.