Exosomes are key mediators of cell-to-cell communication involved in different aspects of the response to ionizing radiation. The functional role of exosomes depends on their molecular cargo, including protein and miRNA content. In this work, we compared the miRNA profile of cells exposed to a high-dose of radiation and the exosomes released by those cells. FaDu cells (derived from human head and neck cancer) were exposed to 2 and 8 Gy doses, exosomes were purified from culture media at 36 h postirradiation using a combination of differential centrifugation, ultrafiltration and precipitation, then microRNA was analyzed using the RNA-seq approach. There were 439 miRNA species quantified, and significant differences in their relative abundance were observed between the cells and exosomes; several low-abundance miRNAs were over-represented while high-abundance miRNA were under-represented in exosomes. There were a few miRNA species markedly affected in irradiated cells and in exosomes released by these cells. However, markedly different radiation-induced effects were observed in both miRNA sets, which could be exemplified by miR-3168 significantly downregulated in cells and upregulated in exosomes. On the other hand, both 2 and 8 Gy radiation doses induced similar effects. Radiation-affected miRNA species present in exosomes are linked to genes involved in the DNA damage and cytokine-mediated response, which may suggest their hypothetical role in the exosome-mediated radiation-induced bystander effect reported elsewhere.

外来体是细胞间通信的关键介体，涉及电离辐射反应的不同方面。外泌体的功能作用取决于它们的分子负荷，包括蛋白质和miRNA含量。在这项工作中，我们比较了暴露于高剂量辐射的细胞的miRNA谱图以及这些细胞释放的外泌体。FaDu细胞（源自人类头颈癌）暴露于2和8 Gy剂量，在辐照后36 h使用差异离心，超滤和沉淀相结合的方法从培养基中纯化外泌体，然后使用RNA-seq分析microRNA方法。量化了439种miRNA种类，并且在细胞和外泌体之间观察到它们的相对丰度有显着差异；在外泌体中，一些低丰度的miRNA含量过高，而高丰度的miRNA含量不足。在受辐照的细胞和这些细胞释放的外泌体中，有几种miRNA种类受到显着影响。但是，在两个miRNA组中均观察到明显不同的辐射诱导效应，这可以通过在细胞中显着下调并在外来体中上调的miR-3168来例证。另一方面，2和8 Gy辐射剂量均引起类似的效果。存在于外泌体中的受辐射影响的miRNA物种与参与DNA损伤和细胞因子介导的反应的基因有关，这可能表明它们在外泌体介导的辐射诱导的旁观者效应中的假设作用。在受辐照的细胞和这些细胞释放的外泌体中，有几种miRNA种类受到显着影响。但是，在两个miRNA组中均观察到明显不同的辐射诱导效应，这可以通过在细胞中显着下调并在外泌体中上调的miR-3168来例证。另一方面，2和8 Gy辐射剂量均引起类似的效果。存在于外泌体中的受辐射影响的miRNA物种与参与DNA损伤和细胞因子介导的反应的基因有关，这可能表明它们在外泌体介导的辐射诱导的旁观者效应中的假设作用。在受辐照的细胞和这些细胞释放的外泌体中，有几种miRNA种类受到显着影响。但是，在两个miRNA组中均观察到明显不同的辐射诱导效应，这可以通过在细胞中显着下调并在外泌体中上调的miR-3168来例证。另一方面，2和8 Gy辐射剂量均引起类似的效果。存在于外泌体中的受辐射影响的miRNA物种与参与DNA损伤和细胞因子介导的反应的基因有关，这可能表明它们在外泌体介导的辐射诱导的旁观者效应中的假设作用。miR-3168可以在细胞中显着下调而在外泌体中上调。另一方面，2和8 Gy辐射剂量均引起类似的效果。存在于外泌体中的受辐射影响的miRNA物种与参与DNA损伤和细胞因子介导的反应的基因有关，这可能表明它们在外泌体介导的辐射诱导的旁观者效应中的假设作用。miR-3168可以在细胞中显着下调而在外泌体中上调。另一方面，2和8 Gy辐射剂量均引起相似的效果。存在于外泌体中的受辐射影响的miRNA物种与参与DNA损伤和细胞因子介导的反应的基因有关，这可能表明它们在外泌体介导的辐射诱导的旁观者效应中的假设作用。