Ionizing radiation regulates long non-coding RNAs in human peripheral blood mononuclear cells.
Ionizing radiation regulates long non-coding RNAs in human peripheral blood mononuclear cells.
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DOI：
10.1093/jrr/rrw111
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发表时间：
2017-03-01
影响因子：
2
通讯作者：
Mildner M
中科院分区：
文献类型：
--
作者：
Beer L;Nemec L;Wagner T;Ristl R;Altenburger LM;Ankersmit HJ;Mildner M
长链非编码RNA（lncRNA）是调节mRNA和microRNA（miRNA）表达的非蛋白质编码转录物，从而控制多个细胞过程，包括基因表达的转录调节、细胞分化和凋亡。电离辐射（IR）是一种强烈的细胞应激源，已知其主要通过激活氧化过程影响受照射细胞的基因表达。IR是否以及如何影响人外周血单核细胞（PBMC）中lncRNA的表达仍然知之甚少。PBMC暴露于IR剂量依赖性地激活p53及其下游靶点p21，最终导致细胞周期停滞和/或凋亡。在低至30戈伊的剂量下，可检测到caspase-3的裂解，这是凋亡细胞死亡过程中的一个特定过程。60 Gy照射的PBMC的转录组分析揭示了多种lncRNA的强烈的时间依赖性调节。在许多未知的lncRNA中，我们还鉴定了Trp 53 cor 1、MEG 3和TUG 1的显著上调，这些蛋白已被证明参与p53介导的细胞周期和凋亡过程的调节。此外，我们在相同的样本中发现了177种受到调节的miRNA，包括几种已知的上调lncRNA的靶点。我们的数据表明，IR剂量依赖性地调节PBMC中广谱lncRNA的表达，这表明lncRNA在响应IR而激活的复杂调节机制中起着至关重要的作用。
Long non-coding RNAs (lncRNAs) are non-protein coding transcripts that modulate mRNA and microRNA (miRNA) expression, thereby controlling multiple cellular processes, including transcriptional regulation of gene expression, cell differentiation and apoptosis. Ionizing radiation (IR), a strong cellular stressor, is known to influence gene expression of irradiated cells, mainly by activation of oxidative processes. Whether and how IR also affects lncRNA expression in human peripheral blood mononuclear cells (PBMCs) is still poorly understood. Exposure of PBMCs to IR dose-dependently activated p53 and its downstream target p21, ultimately leading to cell-cycle arrest and/or apoptosis. Cleavage of caspase-3, a specific process during apoptotic cell death, was detectable at doses as low as 30 Gy. Transcriptome analysis of 60 Gy–irradiated PBMCs revealed a strong time-dependent regulation of a variety of lncRNAs. Among many unknown lncRNAs we also identified a significant upregulation of Trp53cor1, MEG3 and TUG1, which have been shown to be involved in the regulation of cell cycle and apoptotic processes mediated by p53. In addition, we found 177 miRNAs regulated in the same samples, including several miRNAs that are known targets of upregulated lncRNAs. Our data show that IR dose-dependently regulates the expression of a wide spectrum of lncRNAs in PBMCs, suggesting a crucial role for lncRNAs in the complex regulatory machinery activated in response to IR.
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