ArticleCell communication and signaling : CCS2024
Ionizing radiation effects on blood-derived extracellular vesicles: insights into miR-34a-5p-mediated cellular responses and biomarker potential.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Extracellular Vesicles in Diffuse Midline Glioma: Emerging Mediators of Radiation Response and Therapeutic Resistance.Cancers · 2026Review
- Lipid nanoparticle-encapsulated microRNA-192: An anti-inflammatory adjuvant that enhances vaccine efficacy in aged mice.Molecular therapy. Nucleic acids · 2026Article
- Fenofibrate attenuates the adverse effects of radiation on endothelial cells through modulation of ROS-NO signalling and inflammation.Redox biology · 2026Article
- Urinary Biomarkers for Radiation Cystitis: Current Insights and Future Directions.International journal of molecular sciences · 2026Review
- Biomechanical strain alters the microRNA cargo of primary myogenic cell-derived extracellular vesicles associated with a differentiation phenotype.Frontiers in cell and developmental biology · 2026Article
- Extracellular vesicles derived from irradiated tumor cells foster immunosuppressive macrophages formation to promote esophageal squamous cell carcinoma immune evasion.International journal of biological sciences · 2026Article
- Exploring molecular and modular insights into space ionizing radiation effects through heterogeneous gene regulatory networks.NPJ microgravity · 2025Article
- Liver quad culture chip as a model for radiation injury research.Scientific reports · 2025Article
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4 authors.
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Abstract
Adverse effects of ionizing radiation on normal tissues limit the radiation dose in cancer treatment, thereby compromising treatment efficiency. Among the consistently affected non-cancer cells, peripheral blood mononuclear cells (PBMCs) exhibit high radiosensitivity and have the potential to induce systemic effects. PBMC-released extracellular vesicles (EVs), contribute to the communication of such systemic effects. This study aimed to investigate the effects of ionizing radiation on EVs as part of the systemic response of PBMCs in terms of microRNA cargo and biological functions.Therefore, whole blood samples from healthy donors were irradiated ex-vivo (0 Gy, 1 Gy, 2 Gy, 4 Gy) and EVs from PBMCs were isolated after 96 h by PEG precipitation or ultracentrifugation. Candidate microRNAs were examined in PBMC-derived EVs from individual donors. The uptake of membrane-stained fluorescent EVs by different recipient cells was quantified by fluorescence-activated cell sorting analysis. The biological effects of increased miR-34a-5p and of total EVs on recipient cells were assessed.Irradiation of PBMCs induced a dose-dependent upregulation of miR-34a-5p within EVs and PBMCs. However, interindividual differences between donors were noticed in the extent of upregulation, and small EVs displayed more pronounced changes in microRNA levels in comparison to large EVs. Irradiation in presence of the small molecule inhibitor KU-60019 demonstrated that this upregulation is dependent on ATM (Ataxia telangiectasia mutated) activation. Moreover, fibroblasts and keratinocytes were identified as preferred EV recipients. Increased miR-34a-5p levels led to a significant reduction in viability and induction of senescence in keratinocytes but not in fibroblasts, indicating a cell type-specific response.In conclusion, this study further elucidated the complex cellular response of normal tissue after radiation exposure. It confirmed radiation-induced modifications of microRNA expression levels in EVs from PBMCs and identified a robust upregulation of miR-34a-5p in the small EV subfraction, suggesting this microRNA as a potential novel candidate for the development of biomarkers for radiation exposure. Moreover, the different uptake efficiencies observed among specific cell types suggested that EVs induce cell type-specific responses in the intercellular communication of systemic radiation effects.
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