Cross-species conserved miRNA as biomarker of radiation injury over a wide dose range using nonhuman primate model

Multiple accidents in nuclear power plants and the growing concerns about the misuse of radiation exposure in warfare have called for the rapid determination of absorbed radiation doses (RDs). The latest findings about circulating microRNA (miRNAs) using several animal models revealed considerable p...

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Published in:	PloS one Vol. 19; no. 11; p. e0311379
Main Authors:	Chakraborty, Nabarun, Dimitrov, George, Kanan, Swapna, Lawrence, Alexander, Moyler, Candance, Gautam, Aarti, Fatanmi, Oluseyi O, Wise, Stephen Y, Carpenter, Alana D, Hammamieh, Rasha, Singh, Vijay K
Format:	Journal Article
Language:	English
Published:	San Francisco Public Library of Science 21-11-2024 Public Library of Science (PLoS)
Subjects:	Analysis Animal models Artificial intelligence Biology and life sciences Biomarkers Blood transfusions Discrimination DNA methylation Dosimetry Epigenetics Fatalities Health risk assessment Health risks Human bias Irradiation Laboratory animals Medicine and Health Sciences MicroRNA MicroRNAs miRNA Nuclear accidents Nuclear accidents & safety Nuclear energy Nuclear power plants Physical Sciences Post-irradiation Precision medicine Protection and preservation Radiation Radiation dosage Radiation effects Radiation injuries Regression models Research and Analysis Methods Respiratory distress syndrome Translation Wildlife conservation United States > US
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Summary:	Multiple accidents in nuclear power plants and the growing concerns about the misuse of radiation exposure in warfare have called for the rapid determination of absorbed radiation doses (RDs). The latest findings about circulating microRNA (miRNAs) using several animal models revealed considerable promises, although translating this knowledge to clinics remains a major challenge. To address this issue, we randomly divided 36 nonhuman primates (NHPs) into six groups and exposed these groups to six different radiation doses ranging from 6.0–8.5 Gy in increments of 0.5 Gy. Serum samples were collected pre-irradiation as well as three post-irradiation timepoints, namely 1, 2 and 6 days post-total body irradiation (TBI). Generated from a deep sequencing platform, the miRNA reads were multi-variate analyzed to find the differentially expressed putative biomarkers that were linked to RDs, time since irradiation (TSI) and sex. To increase these biomarkers’ translational potential, we aligned the NHP-miRNAs’ sequences and their functional responses to humans following an in-silico routine. Those miRNAs, which were sequentially and functionally conserved between NHPs and humans, were down selected for further analysis. A linear regression model identified miRNA markers that were consistently regulated with increasing RD but independent TSI. Likewise, a set of potential TSI-markers were identified that consistently shifted with increasing TSI, but independent of RD. Additional molecular analysis found a considerable gender bias in the low-ranges of doses when the risk to radiation-induced fatality was low. Bionetworks linked to cell quantity and cell invasion were significantly altered between the survivors and decedents. Using these biomarkers, an assay could be developed to retrospectively determine the RD and TSI with high translational potential. Ultimately, this knowledge can lead to precise and personalized medicine.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Competing Interests: The authors have declared that no competing interests exist.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0311379