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**：核事故中意外暴露于致命辐射是一项重大公共安全关切，当前亟需挖掘辐射生物剂量学（radiation biodosimetry）相关生物标志物，以实现受照人群的分诊分流与重症暴露个体的针对性治疗。**研究目的**：从接受全身照射的小鼠全血样本中，筛选可区分辐射剂量的微小RNA（miRNA）特征标记。**研究方法**：采用X射线对小鼠实施全身照射，照射剂量范围为2 Gy~15 Gy；于照射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；筛选照射组与未照射对照组间的差异表达miRNA，通过特征提取与分类模型预测可区分辐射剂量的miRNA特征标记。**研究结果**：本研究观察到miRNA的表达水平呈现时间与剂量依赖性变化；照射后24小时及48小时为差异表达miRNA数量最多的时间节点。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的特征标记。在全身照射小鼠与非人灵长类动物样本中，均观察到miR-17家族成员及其靶基因的表达变化呈负相关关系。**研究结论**：基于全血的miRNA表达特征标记，可用于大规模伤亡核事故中的辐射暴露风险预测。