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

Abstract

CONTEXT: 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. OBJECTIVE: To identify dose-differentiating miRNA signatures from whole blood samples of whole body irradiated mice. METHODS: 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. RESULTS: 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. CONCLUSION: Whole blood-based miRNA expression signatures might be used for predicting radiation exposures in a mass casualty nuclear incident.