Nature Communications (Jun 2024)
Space radiation damage rescued by inhibition of key spaceflight associated miRNAs
- J. Tyson McDonald,
- JangKeun Kim,
- Lily Farmerie,
- Meghan L. Johnson,
- Nidia S. Trovao,
- Shehbeel Arif,
- Keith Siew,
- Sergey Tsoy,
- Yaron Bram,
- Jiwoon Park,
- Eliah Overbey,
- Krista Ryon,
- Jeffrey Haltom,
- Urminder Singh,
- Francisco J. Enguita,
- Victoria Zaksas,
- Joseph W. Guarnieri,
- Michael Topper,
- Douglas C. Wallace,
- Cem Meydan,
- Stephen Baylin,
- Robert Meller,
- Masafumi Muratani,
- D. Marshall Porterfield,
- Brett Kaufman,
- Marcelo A. Mori,
- Stephen B. Walsh,
- Dominique Sigaudo-Roussel,
- Saida Mebarek,
- Massimo Bottini,
- Christophe A. Marquette,
- Eve Syrkin Wurtele,
- Robert E. Schwartz,
- Diego Galeano,
- Christopher E. Mason,
- Peter Grabham,
- Afshin Beheshti
Affiliations
- J. Tyson McDonald
- Department of Radiation Medicine, Georgetown University School of Medicine
- JangKeun Kim
- Department of Physiology, Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine
- Lily Farmerie
- Vascular Medicine Institute at the University of Pittsburgh Department of Medicine
- Meghan L. Johnson
- Vascular Medicine Institute at the University of Pittsburgh Department of Medicine
- Nidia S. Trovao
- Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health
- Shehbeel Arif
- Center for Data-Driven Discovery in Biomedicine, Children’s Hospital of Philadelphia
- Keith Siew
- London Tubular Centre, Department of Renal Medicine, University College London
- Sergey Tsoy
- Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine
- Yaron Bram
- Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine
- Jiwoon Park
- Department of Physiology, Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine
- Eliah Overbey
- Department of Physiology, Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine
- Krista Ryon
- Department of Physiology, Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine
- Jeffrey Haltom
- The Center for Mitochondrial and Epigenomic Medicine, The Children’s Hospital of Philadelphia
- Urminder Singh
- Bioinformatics and Computational Biology Program, Department of Genetics, Development and Cell Biology, Iowa State University
- Francisco J. Enguita
- Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa
- Victoria Zaksas
- Center for Translational Data Science, University of Chicago
- Joseph W. Guarnieri
- The Center for Mitochondrial and Epigenomic Medicine, The Children’s Hospital of Philadelphia
- Michael Topper
- Departments of Oncology and Medicine and the Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions
- Douglas C. Wallace
- The Center for Mitochondrial and Epigenomic Medicine, The Children’s Hospital of Philadelphia
- Cem Meydan
- Department of Physiology, Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine
- Stephen Baylin
- Departments of Oncology and Medicine and the Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins Medical Institutions
- Robert Meller
- Neuroscience Institute, Department of Neurobiology/ Department of Pharmacology and Toxicology, Morehouse School of Medicine
- Masafumi Muratani
- Transborder Medical Research Center, University of Tsukuba
- D. Marshall Porterfield
- Department of Agricultural and Biological Engineering, Purdue University
- Brett Kaufman
- Vascular Medicine Institute at the University of Pittsburgh Department of Medicine
- Marcelo A. Mori
- Department of Biochemistry and Tissue Biology, Institute of Biology, Universidade Estadual de Campinas
- Stephen B. Walsh
- London Tubular Centre, Department of Renal Medicine, University College London
- Dominique Sigaudo-Roussel
- LBTI- UMR CNRS 5305, Université Claude Bernard Lyon 1
- Saida Mebarek
- ICBMS, UMR5246, CNRS, INSA, CPE-Lyon, Université Claude Bernard Lyon 1
- Massimo Bottini
- Department of Experimental Medicine, University of Rome Tor Vergata
- Christophe A. Marquette
- 3d.FAB, CNRS, INSA, CPE-Lyon, UMR5246, ICBMS, Université Claude Bernard Lyon 1
- Eve Syrkin Wurtele
- Bioinformatics and Computational Biology Program, Department of Genetics, Development and Cell Biology, Iowa State University
- Robert E. Schwartz
- Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine
- Diego Galeano
- Facultad de Ingeniería, Universidad Nacional de Asunción
- Christopher E. Mason
- Department of Physiology, Biophysics and Systems Biology and the WorldQuant Initiative, Weill Cornell Medicine
- Peter Grabham
- Center for Radiological Research, College of Physicians and Surgeons, Columbia University
- Afshin Beheshti
- Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard
- DOI
- https://doi.org/10.1038/s41467-024-48920-y
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 23
Abstract
Abstract Our previous research revealed a key microRNA signature that is associated with spaceflight that can be used as a biomarker and to develop countermeasure treatments to mitigate the damage caused by space radiation. Here, we expand on this work to determine the biological factors rescued by the countermeasure treatment. We performed RNA-sequencing and transcriptomic analysis on 3D microvessel cell cultures exposed to simulated deep space radiation (0.5 Gy of Galactic Cosmic Radiation) with and without the antagonists to three microRNAs: miR-16-5p, miR-125b-5p, and let-7a-5p (i.e., antagomirs). Significant reduction of inflammation and DNA double strand breaks (DSBs) activity and rescue of mitochondria functions are observed after antagomir treatment. Using data from astronaut participants in the NASA Twin Study, Inspiration4, and JAXA missions, we reveal the genes and pathways implicated in the action of these antagomirs are altered in humans. Our findings indicate a countermeasure strategy that can potentially be utilized by astronauts in spaceflight missions to mitigate space radiation damage.
