Research ArticleRADIATION INJURY

Evolutionarily conserved serum microRNAs predict radiation-induced fatality in nonhuman primates

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Science Translational Medicine  01 Mar 2017:
Vol. 9, Issue 379, eaal2408
DOI: 10.1126/scitranslmed.aal2408

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Radiation alert

When a nuclear accident or attack occurs and people are exposed to radiation, a rapid and accurate response is vital for saving lives. In particular, it is important to identify those who had been exposed to radiation at all and to determine which victims are at risk of death or severe injury and require urgent treatment. Fendler et al. studied nonhuman primates who had been exposed to radiation and given a radioprotective drug or placebo, and then analyzed the animals’ blood and developed an miRNA-based classifier. By measuring the expression of five miRNAs (adjusted for gender), the authors were able to identify which primates had been exposed to radiation as well as their chances of survival.

Abstract

Effective planning for the medical response to a radiological or nuclear accident is complex. Because of limited resources for medical countermeasures, the key would be to accurately triage and identify victims most likely to benefit from treatment. We used a mouse model system to provide evidence that serum microRNAs (miRNAs) may effectively predict the impact of radiation on the long-term viability of animals. We had previously used nonhuman primates (NHPs) to demonstrate that this concept is conserved and serum miRNA signatures have the potential to serve as prediction biomarkers for radiation-induced fatality in a human population. We identified a signature of seven miRNAs that are altered by irradiation in both mice and NHPs. Genomic analysis of these conserved miRNAs revealed that there is a combination of seven transcription factors that are predicted to regulate these miRNAs in human, mice, and NHPs. Moreover, a combination of three miRNAs (miR-133b, miR-215, and miR-375) can identify, with nearly complete accuracy, NHPs exposed to radiation versus unexposed NHPs. Consistent with historical data, female macaques appeared to be more sensitive to radiation, but the difference was not significant. Sex-based stratification allowed us to identify an interaction between gender and miR-16-2 expression, which affected the outcome of radiation exposure. Moreover, we developed a classifier based on two miRNAs (miR-30a and miR-126) that can reproducibly predict radiation-induced mortality. Together, we have obtained a five-miRNA composite signature that can identify irradiated macaques and predict their probability of survival.

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