Space radiation damage rescued by inhibition of key spaceflight associated miRNAs

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McDonald, J. Tyson ; Kim, JangKeun ; Farmerie, Lily ; Johnson, Meghan L. ; Trovao, Nidia S. ; Arif, Shehbeel ; Siew, Keith ; Tsoy, Sergey ; Bram, Yaron ; Park, Jiwoon ; Overbey, Eliah ; Ryon, Krista ; Haltom, Jeffrey ; Singh, Urminder ; Enguita, Francisco J. ; Zaksas, Victoria ; Guarnieri, Joseph W. ; Topper, Michael ; Wallace, Douglas C. ; Meydan, Cem ; Baylin, Stephen ; Meller, Robert ; Muratani, Masafumi ; Porterfield, D. Marshall ; Kaufman, Brett ; Mori, Marcelo A. ; Walsh, Stephen B. ; Sigaudo-Roussel, Dominique ; Mebarek, Saida ; Bottini, Massimo ; Marquette, Christophe A. ; Wurtele, Eve Syrkin ; Schwartz, Robert E. ; Galeano, Diego ; Mason, Christopher E. ; Grabham, Peter ; Beheshti, Afshin

• Tipo de documento: Artigo Científico
• Fonte: NATURE COMMUNICATIONS; v. 15, n. 1, p. 23-pg., 2024-06-11.

Resumo

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. In space radiation-exposed cells, targeting specific microRNAs with antagomirs can reduce cardiovascular damage and improve cellular function. Here the authors describe a reduction in inflammation and DNA double-strand break activity within these cells upon antagomir treatment. (AU)

• Processo FAPESP: 21/08354-2 - A ação recíproca do sistema imune e do metabolismo como principal determinante do processo de envelhecimento
• Beneficiário: Marcelo Alves da Silva Mori
• Modalidade de apoio: Auxílio à Pesquisa - Temático