RNA N6-methyladenosine modification-based biomarkers for absorbed ionizing radiation dose estimation

Abstract Radiation triage and biological dosimetry are critical for the medical management of massive potentially exposed individuals following radiological accidents. Here, we performed a genome-wide screening of radiation-responding mRNAs, whose N6-methyladenosine (m6A) levels showed significant a...

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Main Authors: Hongxia Chen, Xi Zhao, Wei Yang, Qi Zhang, Rongjiao Hao, Siao Jiang, Huihui Han, Zuyin Yu, Shuang Xing, Changjiang Feng, Qianqian Wang, Hao Lu, Yuanfeng Li, Cheng Quan, Yiming Lu, Gangqiao Zhou
Format: Article
Language:English
Published: Nature Portfolio 2023-10-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-42665-w
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author Hongxia Chen
Xi Zhao
Wei Yang
Qi Zhang
Rongjiao Hao
Siao Jiang
Huihui Han
Zuyin Yu
Shuang Xing
Changjiang Feng
Qianqian Wang
Hao Lu
Yuanfeng Li
Cheng Quan
Yiming Lu
Gangqiao Zhou
author_facet Hongxia Chen
Xi Zhao
Wei Yang
Qi Zhang
Rongjiao Hao
Siao Jiang
Huihui Han
Zuyin Yu
Shuang Xing
Changjiang Feng
Qianqian Wang
Hao Lu
Yuanfeng Li
Cheng Quan
Yiming Lu
Gangqiao Zhou
author_sort Hongxia Chen
collection DOAJ
description Abstract Radiation triage and biological dosimetry are critical for the medical management of massive potentially exposed individuals following radiological accidents. Here, we performed a genome-wide screening of radiation-responding mRNAs, whose N6-methyladenosine (m6A) levels showed significant alteration after acute irradiation. The m6A levels of three genes, Ncoa4, Ate1 and Fgf22, in peripheral blood mononuclear cells (PBMCs) of mice showed excellent dose-response relationships and could serve as biomarkers of radiation exposure. Especially, the RNA m6A of Ncoa4 maintained a high level as long as 28 days after irradiation. We demonstrated its responsive specificity to radiation, conservation across the mice, monkeys and humans, and the dose-response relationship in PBMCs from cancer patients receiving radiation therapy. Finally, NOCA4 m6A-based biodosimetric models were constructed for estimating absorbed radiation doses in mice or humans. Collectively, this study demonstrated the potential feasibility of RNA m6A in radiation accidents management and clinical applications.
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spelling doaj.art-9b353cd1660d440ebdcb037769508c642023-11-05T12:22:34ZengNature PortfolioNature Communications2041-17232023-10-0114111610.1038/s41467-023-42665-wRNA N6-methyladenosine modification-based biomarkers for absorbed ionizing radiation dose estimationHongxia Chen0Xi Zhao1Wei Yang2Qi Zhang3Rongjiao Hao4Siao Jiang5Huihui Han6Zuyin Yu7Shuang Xing8Changjiang Feng9Qianqian Wang10Hao Lu11Yuanfeng Li12Cheng Quan13Yiming Lu14Gangqiao Zhou15State Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation MedicineState Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation MedicineDepartment of Radiation Oncology, the First Medical Center of Chinese PLA General HospitalState Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation MedicineState Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation MedicineState Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation MedicineState Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation MedicineState Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation MedicineState Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation MedicineDepartment of Thoracic Surgery, the First Medical Center of Chinese PLA General HospitalDepartment of Radiation Oncology, the First Medical Center of Chinese PLA General HospitalState Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation MedicineState Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation MedicineState Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation MedicineState Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation MedicineState Key Laboratory of Proteomics, National Center for Protein Sciences at Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation MedicineAbstract Radiation triage and biological dosimetry are critical for the medical management of massive potentially exposed individuals following radiological accidents. Here, we performed a genome-wide screening of radiation-responding mRNAs, whose N6-methyladenosine (m6A) levels showed significant alteration after acute irradiation. The m6A levels of three genes, Ncoa4, Ate1 and Fgf22, in peripheral blood mononuclear cells (PBMCs) of mice showed excellent dose-response relationships and could serve as biomarkers of radiation exposure. Especially, the RNA m6A of Ncoa4 maintained a high level as long as 28 days after irradiation. We demonstrated its responsive specificity to radiation, conservation across the mice, monkeys and humans, and the dose-response relationship in PBMCs from cancer patients receiving radiation therapy. Finally, NOCA4 m6A-based biodosimetric models were constructed for estimating absorbed radiation doses in mice or humans. Collectively, this study demonstrated the potential feasibility of RNA m6A in radiation accidents management and clinical applications.https://doi.org/10.1038/s41467-023-42665-w
spellingShingle Hongxia Chen
Xi Zhao
Wei Yang
Qi Zhang
Rongjiao Hao
Siao Jiang
Huihui Han
Zuyin Yu
Shuang Xing
Changjiang Feng
Qianqian Wang
Hao Lu
Yuanfeng Li
Cheng Quan
Yiming Lu
Gangqiao Zhou
RNA N6-methyladenosine modification-based biomarkers for absorbed ionizing radiation dose estimation
Nature Communications
title RNA N6-methyladenosine modification-based biomarkers for absorbed ionizing radiation dose estimation
title_full RNA N6-methyladenosine modification-based biomarkers for absorbed ionizing radiation dose estimation
title_fullStr RNA N6-methyladenosine modification-based biomarkers for absorbed ionizing radiation dose estimation
title_full_unstemmed RNA N6-methyladenosine modification-based biomarkers for absorbed ionizing radiation dose estimation
title_short RNA N6-methyladenosine modification-based biomarkers for absorbed ionizing radiation dose estimation
title_sort rna n6 methyladenosine modification based biomarkers for absorbed ionizing radiation dose estimation
url https://doi.org/10.1038/s41467-023-42665-w
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