Characterization of exosome release and extracellular vesicle-associated miRNAs for human bronchial epithelial cells irradiated with high charge and energy ions

摘要: ABSTRACT Exosomes are extracellular vesicles that mediate transport of nucleic acids, proteins, and other molecules. Prior work has implicated exosomes in the transmission radiation nontargeted effects. Here we investigate ability energetic heavy ions, representative species found galactic cosmic rays, to stimulate exosome release from human bronchial epithelial cells vitro. Immortalized (HBEC3-KT F25F) were irradiated with 1.0 Gy high linear energy transfer (LET) 48Ti, 28Si, or 16O 10 Gy low-LET reference γ-rays, collected conditioned media. Preparations characterized by single particle tracking analysis, electron microscopy, immunoblotting for exosomal marker, TSG101. Based on TSG101 levels, irradiation high-LET but not stimulated about 4-fold, relative mock-irradiated controls. The exosome-enriched vesicle preparations contained pro-inflammatory damage-associated molecular patterns, including HSP70 calreticulin. Additionally, miRNA profiling was performed vesicular RNAs using NanoString technology. profile skewed toward a small number have previously been shown be involved cancer initiation progression, miR-1246, miR-1290, miR-23a, miR-205. set 24 miRNAs defined as modestly over-represented HZE ion-irradiated versus cells. Gene enrichment analysis based showed highly significant association nonsmall cell lung cancers.