Introduction:

Acute exposure to ionizing radiation (IR) is hazardous or even lethal. Accurate estimation of the doses of IR exposure is critical to wisely determining the following treatments. Exosomes are nanoscale vesicles harboring biomolecules and mediate the communications among cells and tissues to influence biological processes. Screening out the microRNAs (miRNAs) contained in exosomes as biomarkers can be useful for estimating the IR exposure doses and exploring the correlation between these miRNAs and the occurrence of disease.

Methods:

We treated mice with 2.0, 6.5, and 8.0 Gy doses of IR and collected the mice sera at 0, 24, 48, and 72 hours after exposure. Then, the serum exosomes were isolated by ultracentrifuge and the small RNA portion was extracted for sequencing and the following bioinformatics analysis. Qualitative polymerase chain reaction was performed to validate the potential dose-specific markers.

Results:

Fifty-six miRNAs (31 upregulated, 25 downregulated) were differentially expressed after exposure of the above 3 IR doses and may act as common IR exposure miRNA markers. Bioinformatic analysis also identified several dosage-specific responsive miRNAs. Importantly, IR-induced miR-151-3p and miR-128-3p were significantly and stably increased at 24 hours in different mouse strains with distinct genetic background after exposed to 8.0 Gy of IR.

Conclusion:

Our study shows that miR-151-3p and miR-128-3p can be used as dose-specific biomarkers of 8.0 Gy IR exposure, which can be used to determine the exposure dose by detecting the amount of the 2 miRNAs in serum exosomes.

中文翻译：

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外泌体小 RNA 测序揭示了电离辐射暴露的剂量特异性 miRNA 标记。

介绍：

急性暴露于电离辐射 (IR) 是危险的，甚至是致命的。准确估计 IR 暴露的剂量对于明智地确定以下治疗方法至关重要。外泌体是含有生物分子的纳米级囊泡，可介导细胞和组织之间的通讯以影响生物过程。筛选出作为生物标志物的外泌体中包含的 microRNA (miRNA) 可用于估计 IR 暴露剂量和探索这些 miRNA 与疾病发生之间的相关性。

方法：

我们用 2.0、6.5 和 8.0 Gy 剂量的 IR 治疗小鼠，并在暴露后 0、24、48 和 72 小时收集小鼠血清。然后，通过超速离心机分离血清外泌体，提取小RNA部分进行测序和随后的生物信息学分析。进行定性聚合酶链反应以验证潜在的剂量特异性标志物。

结果：

56 个 miRNA（31 个上调，25 个下调）在上述 3 种 IR 剂量暴露后差异表达，可能作为常见的 IR 暴露 miRNA 标志物。生物信息学分析还确定了几种剂量特异性反应 miRNA。重要的是，在暴露于 8.0 Gy 的 IR 后，IR 诱导的 miR-151-3p 和 miR-128-3p 在具有不同遗传背景的不同小鼠品系中在 24 小时内显着且稳定地增加。

结论：

我们的研究表明 miR-151-3p 和 miR-128-3p 可作为 8.0 Gy IR 暴露的剂量特异性生物标志物，可用于通过检测血清外泌体中 2 种 miRNA 的量来确定暴露剂量。