Bundeswehr Institute of Radiobiology, Neuherbergstr. 11, Munich, 80937, Germany.
Institut de Recherche Biomedicale des Armees, Bretigny-sur-Orge, 91220, France.
Sci Rep. 2018 Oct 18;8(1):15353. doi: 10.1038/s41598-018-33544-2.
We examined the transcriptome/post-transcriptome for persistent gene expression changes after radiation exposure in a baboon model. Eighteen baboons were irradiated with a whole body equivalent dose of 2.5 or 5 Gy. Blood samples were taken before, 7, 28 and 75-106 days after radiation exposure. Stage I was a whole genome screening for mRNA combined with a qRT-PCR platform for detection of 667 miRNAs. Candidate mRNAs and miRNAs differentially up- or down-regulated in stage I were chosen for validation in stage II using the remaining samples. Only 12 of 32 candidate genes provided analyzable results with two mRNAs showing significant 3-5-fold differences in gene expression over the reference (p < 0.0001). From 667 candidate miRNAs, 290 miRNA were eligible for analysis with 21 miRNAs independently validated using qRT-PCR. These miRNAs showed persistent expression changes on each day and over days 7-106 days after exposure (n = 7). In particular miR-212 involved in radiosensitivity and immune modulation appeared persistently and 48-77-fold up-regulated over the entire time period. We are finally trying to put our results into a context of clinical implications and provide possible hints on underlying molecular mechanisms to be examined in future studies.
我们研究了辐射暴露后狒狒模型中持久基因表达变化的转录组/转录后组。18 只狒狒接受全身等效剂量为 2.5 或 5Gy 的照射。在辐射暴露前、7、28 和 75-106 天后采集血样。第 I 阶段是对 mRNA 进行全基因组筛选，并结合 qRT-PCR 平台检测 667 个 miRNAs。在第 I 阶段选择差异上调或下调的候选 mRNAs 和 miRNAs，用于使用其余样本在第 II 阶段进行验证。只有 32 个候选基因中的 12 个提供了可分析的结果，其中两个基因的表达水平相对于参考值显著差异 3-5 倍（p<0.0001）。从 667 个候选 miRNA 中，有 290 个 miRNA 有资格进行分析，其中 21 个 miRNA 独立使用 qRT-PCR 进行验证。这些 miRNA 在暴露后第 7-106 天每天和多天都表现出持续的表达变化（n=7）。特别是 miR-212 参与放射敏感性和免疫调节，持续上调 48-77 倍。我们最终试图将我们的结果置于临床意义的背景下，并为潜在的分子机制提供可能的提示，以在未来的研究中进行检查。
