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Sci Transl Med. 2017 Mar 1;9(379). pii: eaal2408. doi: 10.1126/scitranslmed.aal2408.

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

Author information

1
Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz 91-738, Poland.
2
Department of Radiation Oncology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
3
Medical Gynecologic Oncology Program, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
4
Department of Radiation Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10461, USA. dipanjan_chowdhury@dfci.harvard.edu vijay.singh@usuhs.edu cguha@montefiore.org.
5
Department of Pathology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10461, USA.
6
Department of Pharmacology and Experimental Therapeutics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. dipanjan_chowdhury@dfci.harvard.edu vijay.singh@usuhs.edu cguha@montefiore.org.
7
Armed Forces Radiobiology Research Institute, Bethesda, MD 20814, USA.
8
Department of Radiation Oncology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02215, USA. dipanjan_chowdhury@dfci.harvard.edu vijay.singh@usuhs.edu cguha@montefiore.org.

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.

PMID:
28251902
PMCID:
PMC5441546
DOI:
10.1126/scitranslmed.aal2408
[Indexed for MEDLINE]
Free PMC Article

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