Plasma miRNAome Profiling Reveals Candidate Biomarkers for Low- and High-Dose Whole-Body Ionizing Radiation Exposure

Objective: MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression and remain stable in biological fluids, even under harsh conditions. Their stability and responsiveness to environmental stressors make them strong candidates for radiation biodosimetry. This study aimed to (1) establish a robust in vivo pipeline for miRNAome profiling and (2) identify plasma-based miRNA biomarkers of ionizing radiation at low and high doses. Methods: BALB/c mice were exposed to sham, 100 mGy, or 2 Gy of X-rays. Plasma was collected 6 h post-irradiation. Total RNA was extracted, and next-generation sequencing was used to profile the plasma miRNAome. Differentially expressed miRNAs were identified relative to sham controls, and selected candidates were validated using RT-qPCR. Results: A total of 630 unique miRNAs were detected. High-dose exposure (2 Gy) significantly upregulated 14 and downregulated 5 miRNAs. Seven miRNAs were significantly induced at 100 mGy, including miR-126a-5p and miR-133a-3p, which were exclusive to low-dose exposure. Five miRNAs were shared between both doses, indicating dose-independent responses. RT-qPCR confirmed expression trends. Conclusion: This study identified distinct and shared circulating miRNA signatures for low- and high-dose radiation exposure. These findings support the potential of miRNAs as minimally invasive, dose-stratified biomarkers for radiation biodosimetry.