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

Wojciech Fendler, Beata Malachowska, Khyati Meghani, Panagiotis A. Konstantinopoulos, Chandan Guha, Vijay K. Singh, Dipanjan Chowdhury

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbereaal2408
JournalScience Translational Medicine
Volume9
Issue number379
DOIs
StatePublished - Mar 1 2017

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MicroRNAs
Primates
Radiation
Serum
Macaca
Radioactive Hazard Release
Triage
Transcription Factors
Biomarkers
Survival
Mortality
Population

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Fendler, W., Malachowska, B., Meghani, K., Konstantinopoulos, P. A., Guha, C., Singh, V. K., & Chowdhury, D. (2017). Evolutionarily conserved serum microRNAs predict radiation-induced fatality in nonhuman primates. Science Translational Medicine, 9(379), [eaal2408]. https://doi.org/10.1126/scitranslmed.aal2408

Evolutionarily conserved serum microRNAs predict radiation-induced fatality in nonhuman primates. / Fendler, Wojciech; Malachowska, Beata; Meghani, Khyati; Konstantinopoulos, Panagiotis A.; Guha, Chandan; Singh, Vijay K.; Chowdhury, Dipanjan.

In: Science Translational Medicine, Vol. 9, No. 379, eaal2408, 01.03.2017.

Research output: Contribution to journalArticle

Fendler, W, Malachowska, B, Meghani, K, Konstantinopoulos, PA, Guha, C, Singh, VK & Chowdhury, D 2017, 'Evolutionarily conserved serum microRNAs predict radiation-induced fatality in nonhuman primates', Science Translational Medicine, vol. 9, no. 379, eaal2408. https://doi.org/10.1126/scitranslmed.aal2408
Fendler, Wojciech ; Malachowska, Beata ; Meghani, Khyati ; Konstantinopoulos, Panagiotis A. ; Guha, Chandan ; Singh, Vijay K. ; Chowdhury, Dipanjan. / Evolutionarily conserved serum microRNAs predict radiation-induced fatality in nonhuman primates. In: Science Translational Medicine. 2017 ; Vol. 9, No. 379.
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