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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.
Keywords:
Acknowledgements
We thank SRI International, USA (Study no. R019-16) and CiToxLAB, Canada (Study no. 2017-2243) for providing the non-human primate samples. The authors thank Patricia Rivera-Solis and Katherine Wilsdon for their excellent technical assistance.
Disclosure statement
No potential conflict of interest was reported by the authors.