Microarray analysis of miRNA expression profiles following whole body irradiation in a mouse model

<b>Context:</b> Accidental exposure to life-threatening radiation in a nuclear event is a major concern; there is an enormous need for identifying biomarkers for radiation biodosimetry to triage populations and treat critically exposed individuals. <b>Objective:</b> To identify dose-differentiating miRNA signatures from whole blood samples of whole body irradiated mice. <b>Methods:</b> Mice were whole body irradiated with X-rays (2 Gy–15 Gy); blood was collected at various time-points post-exposure; total RNA was isolated; miRNA microarrays were performed; miRNAs differentially expressed in irradiated vs. unirradiated controls were identified; feature extraction and classification models were applied to predict dose-differentiating miRNA signature. <b>Results:</b> We observed a time and dose responsive alteration in the expression levels of miRNAs. Maximum number of miRNAs were altered at 24-h and 48-h time-points post-irradiation. A 23-miRNA signature was identified using feature selection algorithms and classifier models. An inverse correlation in the expression level changes of miR-17 members, and their targets were observed in whole body irradiated mice and non-human primates. <b>Conclusion:</b> Whole blood-based miRNA expression signatures might be used for predicting radiation exposures in a mass casualty nuclear incident.

<b>背景：</b>核事件中意外暴露于危及生命的辐射是一项重大公共安全关切；当前亟需鉴定辐射生物剂量学的生物标志物，以实现人群分流并对重症暴露个体开展救治。<b>研究目的：</b>从全身辐照小鼠的全血样本中筛选可区分辐射剂量的微小RNA（miRNA）特征。<b>方法：</b>对小鼠实施全身X射线辐照，辐照剂量范围为2 Gy至15 Gy；于辐照后不同时间点采集血液样本，提取总RNA并开展miRNA微阵列检测；筛选辐照组与未辐照对照组间差异表达的miRNA，通过特征提取与分类模型预测可区分辐射剂量的miRNA特征。<b>结果：</b>本研究观察到miRNA的表达水平呈现时间与剂量依赖性变化。辐照后24小时与48小时时间点的差异表达miRNA数量最多。通过特征选择算法与分类器模型，筛选得到包含23个miRNA的特征集。在全身辐照小鼠与非人灵长类动物中，均观察到miR-17家族成员的表达变化与其靶基因的表达变化呈负相关。<b>结论：</b>基于全血的miRNA表达特征可用于大规模伤亡核事件中的辐射暴露剂量预测。