Center for Radiological Research, Department of Radiation Oncology, Columbia University Medical Center, New York, NY 10032, USA.
Int J Radiat Oncol Biol Phys. 2011 Jun 1;80(2):549-57. doi: 10.1016/j.ijrobp.2010.12.061. Epub 2011 Mar 21.
MicroRNAs (miRNAs), a class of noncoding small RNAs that regulate gene expression, are involved in numerous physiologic processes in normal and malignant cells. Our in vivo study measured miRNA and gene expression changes in human blood cells in response to ionizing radiation, to develop miRNA signatures that can be used as biomarkers for radiation exposure.
Blood from 8 radiotherapy patients in complete remission 1 or 2 was collected immediately before and 4 hours after total body irradiation with 1.25 Gy x-rays. Both miRNA and gene expression changes were measured by means of quantitative polymerase chain reaction and microarray hybridization, respectively. Hierarchic clustering, multidimensional scaling, class prediction, and gene ontology analysis were performed to investigate the potential of miRNAs to serve as radiation biomarkers and to elucidate their likely physiologic roles in the radiation response.
The expression levels of 45 miRNAs were statistically significantly upregulated 4 hours after irradiation with 1.25 Gy x-rays, 27 of them in every patient. Nonirradiated and irradiated samples form separate clusters in hierarchic clustering and multidimensional scaling. Out of 223 differentially expressed genes, 37 were both downregulated and predicted targets of the upregulated miRNAs. Paired and unpaired miRNA-based classifiers that we developed can predict the class membership of a sample with unknown irradiation status, with accuracies of 100% when all 45 upregulated miRNAs are included. Both miRNA control of and gene involvement in biologic processes such as hemopoiesis and the immune response are increased after irradiation, whereas metabolic processes are underrepresented among all differentially expressed genes and the genes controlled by miRNAs.
Exposure to ionizing radiation leads to the upregulation of the expression of a considerable proportion of the human miRNAome of peripheral blood cells. These miRNA expression signatures can be used as biomarkers of radiation exposure.
MicroRNAs（miRNAs）是一类非编码的小分子 RNA，可调节基因表达，参与正常和恶性细胞中的许多生理过程。本体内研究测量了人类血细胞中 miRNA 和基因表达在受到电离辐射后的变化，以开发可作为辐射暴露生物标志物的 miRNA 特征。
从 8 例完全缓解 1 或 2 例的放疗患者中采集血液，分别在全身照射 1.25 Gy X 射线前和 4 小时后。分别采用定量聚合酶链反应和微阵列杂交来测量 miRNA 和基因表达变化。进行层次聚类、多维尺度分析、分类预测和基因本体分析，以研究 miRNA 作为辐射生物标志物的潜力，并阐明它们在辐射反应中的可能生理作用。
在接受 1.25 Gy X 射线照射 4 小时后，45 种 miRNA 的表达水平统计学上显著上调，27 种 miRNA 在每位患者中均上调。在层次聚类和多维尺度分析中，未照射和照射的样本形成单独的聚类。在 223 个差异表达基因中，有 37 个基因既是下调基因，也是上调 miRNA 的预测靶基因。我们开发的基于配对和非配对 miRNA 的分类器可以预测未知照射状态的样本的类别归属，当包含所有 45 个上调 miRNA 时，准确率为 100%。miRNA 对生物过程的控制和基因参与，如造血和免疫反应，在照射后增加，而代谢过程在所有差异表达基因和 miRNA 控制的基因中代表性不足。
电离辐射会导致外周血单个核细胞中人类 miRNA 组的表达上调。这些 miRNA 表达特征可作为辐射暴露的生物标志物。
