Proton radiation-induced miRNA signatures in mouse blood: Characterization and comparison with ⁵⁶Fe-ion and gamma radiation

Abstract

Purpose: Previously, we showed that microRNA (miRNA) signatures derived from the peripheral blood of mice are highly specific for both radiation energy (γ-rays or high linear energy transfer [LET] ⁵⁶Fe ions) and radiation dose. Here, we investigate to what extent miRNA expression signatures derived from mouse blood can be used as biomarkers for exposure to 600 MeV proton radiation.

Materials and methods: We exposed mice to 600 MeV protons, using doses of 0.5 or 1.0 Gy, isolated total RNA at 6 h or 24 h after irradiation, and used quantitative real-time polymerase chain reaction (PCR) to determine the changes in miRNA expression. Results: A total of 26 miRNA were differentially expressed after proton irradiation, in either one (77%) or multiple conditions (23%). Statistical classifiers based on proton, γ, and ⁵⁶Fe-ion miRNA expression signatures predicted radiation type and proton dose with accuracies of 81% and 88%, respectively. Importantly, gene ontology analysis for proton-irradiated cells shows that genes targeted by radiation-induced miRNA are involved in biological processes and molecular functions similar to those controlled by miRNA in γ ray- and ⁵⁶Fe-irradiated cells. Conclusions: Mouse blood miRNA signatures induced by proton, γ, or ⁵⁶Fe irradiation are radiation type- and dose-specific. These findings underline the complexity of the miRNA-mediated radiation response.

Keywords:

• miRNA
• protons
• biodosimetry
• high-LET radiation
• class prediction
• gene ontology analysis