Exosomal Small RNA Sequencing Uncovers Dose-Specific MiRNA Markers for Ionizing Radiation Exposure

Abstract

Introduction: Acute exposure to ionizing radiation (IR) is hazardous or even lethal. Accurate estimation of the doses of IR exposure is critical to wisely determining the following treatments. Exosomes are nanoscale vesicles harboring biomolecules and mediate the communications among cells and tissues to influence biological processes. Screening out the microRNAs (miRNAs) contained in exosomes as biomarkers can be useful for estimating the IR exposure doses and exploring the correlation between these miRNAs and the occurrence of disease. Methods: We treated mice with 2.0, 6.5, and 8.0 Gy doses of IR and collected the mice sera at 0, 24, 48, and 72 hours after exposure. Then, the serum exosomes were isolated by ultracentrifuge and the small RNA portion was extracted for sequencing and the following bioinformatics analysis. Qualitative polymerase chain reaction was performed to validate the potential dose-specific markers. Results: Fifty-six miRNAs (31 upregulated, 25 downregulated) were differentially expressed after exposure of the above 3 IR doses and may act as common IR exposure miRNA markers. Bioinformatic analysis also identified several dosage-specific responsive miRNAs. Importantly, IR-induced miR-151-3p and miR-128-3p were significantly and stably increased at 24 hours in different mouse strains with distinct genetic background after exposed to 8.0 Gy of IR. Conclusion: Our study shows that miR-151-3p and miR-128-3p can be used as dose-specific biomarkers of 8.0 Gy IR exposure, which can be used to determine the exposure dose by detecting the amount of the 2 miRNAs in serum exosomes.