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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| Format: | Article |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0311379 |
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| author | Nabarun Chakraborty George Dimitrov Swapna Kanan Alexander Lawrence Candance Moyler Aarti Gautam Oluseyi O Fatanmi Stephen Y Wise Alana D Carpenter Rasha Hammamieh Vijay K Singh |
| author_facet | Nabarun Chakraborty George Dimitrov Swapna Kanan Alexander Lawrence Candance Moyler Aarti Gautam Oluseyi O Fatanmi Stephen Y Wise Alana D Carpenter Rasha Hammamieh Vijay K Singh |
| author_sort | Nabarun Chakraborty |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b3572931517d4e53aede2a1b9c530b5a |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-b3572931517d4e53aede2a1b9c530b5a2025-08-20T02:22:36ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011911e031137910.1371/journal.pone.0311379Cross-species conserved miRNA as biomarker of radiation injury over a wide dose range using nonhuman primate model.Nabarun ChakrabortyGeorge DimitrovSwapna KananAlexander LawrenceCandance MoylerAarti GautamOluseyi O FatanmiStephen Y WiseAlana D CarpenterRasha HammamiehVijay K SinghMultiple 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.https://doi.org/10.1371/journal.pone.0311379 |
| spellingShingle | Nabarun Chakraborty George Dimitrov Swapna Kanan Alexander Lawrence Candance Moyler Aarti Gautam Oluseyi O Fatanmi Stephen Y Wise Alana D Carpenter Rasha Hammamieh Vijay K Singh Cross-species conserved miRNA as biomarker of radiation injury over a wide dose range using nonhuman primate model. PLoS ONE |
| title | Cross-species conserved miRNA as biomarker of radiation injury over a wide dose range using nonhuman primate model. |
| title_full | Cross-species conserved miRNA as biomarker of radiation injury over a wide dose range using nonhuman primate model. |
| title_fullStr | Cross-species conserved miRNA as biomarker of radiation injury over a wide dose range using nonhuman primate model. |
| title_full_unstemmed | Cross-species conserved miRNA as biomarker of radiation injury over a wide dose range using nonhuman primate model. |
| title_short | Cross-species conserved miRNA as biomarker of radiation injury over a wide dose range using nonhuman primate model. |
| title_sort | cross species conserved mirna as biomarker of radiation injury over a wide dose range using nonhuman primate model |
| url | https://doi.org/10.1371/journal.pone.0311379 |
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