The Rat microRNA body atlas; Evaluation of the microRNA content of rat organs through deep sequencing and characterization of pancreas enriched miRNAs as biomarkers of pancreatic toxicity in the rat and dog.
The Rat microRNA body atlas; Evaluation of the microRNA content of rat organs through deep sequencing and characterization of pancreas enriched miRNAs as biomarkers of pancreatic toxicity in the rat and dog.
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DOI：
10.1186/s12864-016-2956-z
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发表时间：
2016-08-30
期刊：
影响因子：
4.4
通讯作者：
Watson DE
中科院分区：
文献类型：
--
作者：
Smith A;Calley J;Mathur S;Qian HR;Wu H;Farmen M;Caiment F;Bushel PR;Li J;Fisher C;Kirby P;Koenig E;Hall DG;Watson DE
微小RNA（miRNA）是约19-25个核苷酸长的RNA分子，其通过掺入RNA诱导沉默复合物（RISC）中抑制mRNA的翻译或降解来微调基因表达。MicroRNA在血清和血浆中稳定，在多种体液中可检测，在兽医物种和人类中保守，并以组织特异性方式表达。它们可以在动物和人类的循环中以低浓度检测到，从而产生了利用miRNA作为组织损伤的基于血清和/或血浆的生物标志物的兴趣。啮齿类动物中的microRNA组织分析已经发表，但使用微阵列或qPCR技术进行miRNA检测的毒理学关注器官的样本数量不足。在这里，我们传授了一个改进的大鼠microRNA体图谱，包括21和23个组织的毒理学利益分别从雄性和雌性Sprague道利大鼠，使用Illumina miRNA测序。几位作者创建了一个狗的miRNA体图谱，我们合作使用两个物种在雨蛙素毒性研究中测试大鼠和狗胰腺中保守的miRNA。一个丰富的数据集，更有力地定义了组织特异性和富集配置文件的先前公布的和未发现的大鼠miRNA。我们从miRBase中生成了1，927个序列，映射到大鼠、小鼠和人类中的成熟miRNA，并发现了额外的1，162个大鼠miRNA，与miRBase版本21中当前的大鼠miRNA数量相比。鉴定组织特异性和富集的miRNA，并通过qPCR验证这些miRNA的子集的组织特异性或富集。作为这种方法的力量的一个例子，我们已经进行了大鼠和狗胰腺毒性研究，并检查了在每个物种的血清中大鼠和狗之间保守的一些组织特异性和富集的miRNA的水平。研究表明，保守的组织特异性/富集的miR-216 a-5 p、375- 3 p、148 a-3 p、216 b-5 p和141- 3 p是大鼠和狗中胰腺损伤的候选生物标志物。大鼠和犬的microRNA体图谱可用于鉴定2种毒理学相关物种中器官毒性的新候选miRNA生物标志物。本文的在线版本（doi：10.1186/s12864-016-2956-z）包含补充材料，可供授权用户使用。
MicroRNAs (miRNA) are ~19–25 nucleotide long RNA molecules that fine tune gene expression through the inhibition of translation or degradation of the mRNA through incorporation into the RNA induced silencing complex (RISC). MicroRNAs are stable in the serum and plasma, are detectable in a wide variety of body fluids, are conserved across veterinary species and humans and are expressed in a tissue specific manner. They can be detected at low concentrations in circulation in animals and humans, generating interest in the utilization of miRNAs as serum and/or plasma based biomarkers of tissue injury. MicroRNA tissue profiling in rodents has been published, but sample an insufficient number of organs of toxicologic interest using microarray or qPCR technologies for miRNA detection. Here we impart an improved rat microRNA body atlas consisting of 21 and 23 tissues of toxicologic interest from male and female Sprague Dawley rats respectively, using Illumina miRNA sequencing. Several of the authors created a dog miRNA body atlas and we collaborated to test miRNAs conserved in rat and dog pancreas in caerulein toxicity studies utilizing both species. A rich data set is presented that more robustly defines the tissue specificity and enrichment profiles of previously published and undiscovered rat miRNAs. We generated 1,927 sequences that mapped to mature miRNAs in rat, mouse and human from miRBase and discovered an additional 1,162 rat miRNAs as compared to the current number of rat miRNAs in miRBase version 21. Tissue specific and enriched miRNAs were identified and a subset of these miRNAs were validated by qPCR for tissue specificity or enrichment. As an example of the power of this approach, we have conducted rat and dog pancreas toxicity studies and examined the levels of some tissue specific and enriched miRNAs conserved between rat and dog in the serum of each species. The studies demonstrate that conserved tissue specific/enriched miRs-216a-5p, 375-3p, 148a-3p, 216b-5p and 141-3p are candidate biomarkers of pancreatic injury in the rat and dog. A microRNA body atlas for rat and dog was useful in identifying new candidate miRNA biomarkers of organ toxicity in 2 toxicologically relevant species. The online version of this article (doi:10.1186/s12864-016-2956-z) contains supplementary material, which is available to authorized users.
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影响因子：
1.2
作者：
Boone, L;Meyer, D;Jordan, H
通讯作者：
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影响因子：
13.5
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作者：
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