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.

背景：核事件中意外暴露于危及生命的辐射是重大公共安全隐患；当前亟需开发辐射生物剂量学（radiation biodosimetry）相关生物标志物，以实现受照人群的分级分诊，并对重症受照个体实施精准诊疗。
研究目的：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（microRNA，miRNA）特征谱。
实验方法：采用X射线对小鼠进行全身辐照，辐照剂量范围为2 Gy~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（miRNA microarray）检测；筛选辐照组与未辐照对照组间的差异表达miRNA；通过特征提取与分类模型，最终筛选得到可区分辐射剂量的miRNA特征谱。
实验结果：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小时及48小时为miRNA表达差异最为显著的时间节点。通过特征选择算法与分类模型，本研究筛选得到包含23个miRNA的特征谱。在全身辐照小鼠与非人灵长类动物模型中，miR-17家族成员及其靶基因的表达变化呈显著负相关关系。
研究结论：基于全血的miRNA表达特征谱，可应用于大规模核事故中的辐射暴露风险预测与评估。