Circulating microRNAs as Biomarkers of Radiation Exposure: A Systematic Review and Meta-Analysis

Purpose MicroRNAs (miRNAs) were hypothesized to be robust and easily measured biomarkers of radiation exposure, which has led to multiple studies in various clinical and experimental scenarios. We sought to identify evolutionary conserved, radiation-induced circulating miRNAs through a multispecies, integrative systematic review and meta-analysis of miRNAs in radiation. Methods and Materials The systematic review was registered in the PROSPERO database (ID: 81701). We downloaded a list of studies with the query: (circulating OR plasma OR serum) AND (miRNA or microRNA) AND (radiat* OR radiotherapy OR irradiati*) from MEDLINE (103 studies), EMBASE (364 studies), and Cochrane Database of Systematic Reviews (0 studies). After deleting 116 duplicates, the remaining 351 abstracts were reviewed. Inclusion criteria were experimental study; human, mice, rat or nonhuman primate study; and serum or plasma miRNA expression measured before and after radiation exposure. Results The screening procedure yielded 62 research studies. After verification, 30 articles contained data on miRNA expression change after irradiation. Thus, we obtained a database of 131 miRNAs from 96 pairwise post-/preirradiation comparisons reporting 2508 fold changes (FCs) of circulating miRNAs. The meta-analysis showed 28 miRNAs with significant radiation-induced change of their expression in the serum. In metaregression analysis, 7 miRNAs—miR-150 (FC = 0.40; 95% confidence interval [CI], 0.35-0.45), miR-29a (FC = 0.87; 95% CI, 0.79-0.96), miR-29b (FC = 0.85; 95% CI, 0.76-0.96), miR-30c (FC = 1.19; 95% CI, 1.09-1.30), miR-200b (FC = 1.34; 95% CI, 1.21-1.48), miR-320a (FC = 1.13; 95% CI, 1.05-1.23), and miR-30a (FC = 1.18; 95% CI, 1.07-1.30)—significantly correlated with either total or fraction dose of radiation. Additionally, miR-150, miR-320a, miR-200b, and miR-30c correlated significantly with time elapsed since irradiation. Conclusions Circulating miRNAs reflect the impact of ionizing radiation irrespective of the studied species, often in a dose-dependent manner. This makes circulating miRNAs promising biomarkers of radiation exposure.