RNA Profiling Reveals a Common Mechanism of Histone Gene Downregulation and Complementary Effects for Radioprotectants in Response to Ionizing Radiation.
RNA Profiling Reveals a Common Mechanism of Histone Gene Downregulation and Complementary Effects for Radioprotectants in Response to Ionizing Radiation.
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RNA 分析揭示了组蛋白基因下调的常见机制以及放射防护剂响应电离辐射的互补作用
DOI：
10.1177/1559325820968433
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Zheng X
中科院分区：
文献类型：
--
作者：
Ge C;Su F;Fu H;Wang Y;Tian B;Liu B;Zhu J;Ding Y;Zheng X
大剂量电离辐射(IR)改变非编码RNA(NcRNAs)的表达水平。然而，ncRNAs和mRNAs在辐射防护剂的辐射防护中的作用尚不清楚。应用基因芯片技术检测经氨磷汀、CBLB502和尼尔雌醇处理的受照小鼠骨髓中的microRNA(MiRNA)、Long ncRNA(LncRNA)和mRNA的表达谱。差异表达的mRNAs通过基因本体论和京都百科全书的基因和基因组途径分析进行功能注释。部分组蛋白簇基因通过实时荧光定量聚合酶链式反应进行验证，并通过生存分析监测辐射防护剂组合的效果。我们发现，这些辐射防护剂增加了lncRNAs和mRNAs的诱导。与氨磷汀和CBLB502相似，但与尼尔雌醇不同，miRNA、lncRNA和mRNA的表达模式相似。这些辐射防护剂对IR诱导的miRNAs、lncRNAs和mRNAs表现出相反的作用，而诱导IR后常见的组蛋白基因下调，主要是通过核小体组装和相关的信号通路。值得注意的是，尼尔雌醇的效果与阿米斯汀或CBLB502的效果显著互补；低剂量的药物组合在预处理的小鼠中产生了更好的辐射防护效果。因此，我们介绍了辐射防护剂对组蛋白基因的下调，以及miRNA、lncRNA和mRNA的生物学功能，以解释辐射防护的机制。
High-dose ionizing radiation (IR) alters the expression levels of non-coding RNAs (ncRNAs). However, the roles of ncRNAs and mRNAs in mediating radiation protection by radioprotectants remain unknown. Microarrays were used to determine microRNA (miRNA), long ncRNA (lncRNA), and mRNA expression profiles in the bone marrow of irradiated mice pretreated with amifostine, CBLB502, and nilestriol. Differentially expressed mRNAs were functionally annotated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Some histone cluster genes were validated by real-time PCR, and the effects of radioprotectant combinations were monitored by survival analysis. We found that these radioprotectants increased the induction of lncRNAs and mRNAs. miRNA, lncRNA, and mRNA expression patterns were similar with amifostine and CBLB502, but not nilestriol. The radioprotectants exhibited mostly opposite effects against IR-induced miRNAs, lncRNAs, and mRNAs while inducing a common histone gene downregulation following IR, mainly via nucleosome assembly and related signaling pathways. Notably, the effects of nilestriol significantly complemented those of amisfostine or CBLB502; low-dose drug combinations resulted in better radioprotective effects in pretreated mice. Thus, we present histone gene downregulation by radioprotectants, together with the biological functions of miRNA, lncRNA, and mRNA, to explain the mechanism underlying radioprotection.
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影响因子：
2
作者：
Beer L;Nemec L;Wagner T;Ristl R;Altenburger LM;Ankersmit HJ;Mildner M
通讯作者：
Mildner M
DOI：
10.1124/jpet.112.196071
发表时间：
2012-11-01
影响因子：
3.5
作者：
Krivokrysenko, Vadim I.;Shakhov, Alexander N.;Feinstein, Elena
通讯作者：
Feinstein, Elena
DOI：
10.1038/ijo.2015.170
发表时间：
2016-01
期刊：
International journal of obesity (2005)
影响因子：
--
作者：
Deiuliis JA
通讯作者：
Deiuliis JA
影响因子：
3.7
作者：
Girardi C;De Pittà C;Casara S;Sales G;Lanfranchi G;Celotti L;Mognato M
通讯作者：
Mognato M
影响因子：
3.4
作者：
Aryankalayil MJ;Chopra S;Levin J;Eke I;Makinde A;Das S;Shankavaram U;Vanpouille-Box C;Demaria S;Coleman CN
通讯作者：
Coleman CN