Space radiation damage rescued by inhibition of key spaceflight associated miRNAs.
J Tyson McDonaldJang-Keun KimLily FarmerieMeghan L JohnsonNídia Sequeira TrovãoShehbeel ArifKeith SiewSergey TsoyYaron BramJiwoon ParkEliah G OverbeyKrista RyonJeffrey HaltomUrminder SinghFrancisco Javier EnguitaViktorija ZaksasJoseph W GuarnieriMichael TopperDouglas C WallaceCem MeydanStephen B BaylinRobert MellerMasafumi MurataniDavid Marshall PorterfieldBrett A KaufmanMarcelo Alves da Silva MoriStephen B WalshDominique Sigaudo-RousselSaida MebarekMassimo BottiniChristophe A MarquetteEve Syrkin WurteleRobert E SchwartzDiego GaleanoChristopher E MasonPeter GrabhamAfshin BehestiPublished in: Nature communications (2024)
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.