We investigated the responses of microRNAs (miRNAs) using mouse embryonic stem cells (mESCs) exposed to nine chemicals (bis(2-ethylhexyl)phthalate, p-cresol, p-dichlorobenzene, phenol, pyrocatecol, chloroform, tri-n-butyl phosphate, trichloroethylene, and benzene), which are listed as "Class I Designated Chemical Substances" from the Japan Pollutant Release and Transfer Register. Using deep sequencing analysis (RNA-seq), several miRNAs were identified that show a substantial response to general chemical toxicity (i.e., to these nine chemicals considered as a group) and several miRNA biomarkers that show a substantial and specific response to benzene. The functions of the identified miRNAs were investigated in accordance with Gene Ontology terms of their predicted target genes, indicating regulation of cellular processes. We compared the results with those for the long non-coding RNAs (ncRNAs) and mRNAs reported in our previous studies in addition to previously identified miRNAs that are either up- or down-regulated in response to the benzene as stimuli. We also observed that the changes in expression of miRNAs were smaller than those for long ncRNAs and mRNAs. Taken together the current and previous results revealed that toxic chemical stimuli regulate the expression of miRNAs. We believe that the use of miRNAs, including the thus identified miRNAs, as biomarkers contribute to predicting the potential toxicity of particular chemicals or identifying human individuals that have been exposed to chemical hazards.

中文翻译：

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通过RNA深度测序分析在小鼠胚胎干细胞中鉴定出用于化学危险性筛选的MicroRNA生物标记。

我们使用暴露于九种化学物质（邻苯二甲酸双（2-乙基己基）酯，对甲酚，对二氯苯，苯酚，邻苯二酚，氯仿，三正丁基磷酸酯）的小鼠胚胎干细胞（mESC），研究了microRNA（miRNA）的响应（三氯乙烯和苯）被日本污染物排放和转移登记簿列为“ I类指定化学物质”。使用深度测序分析（RNA-seq），鉴定了对一般化学毒性（即对这9种化学物质视为一个组）显示出实质性反应的几种miRNA，以及对苯产生了实质性和特异性反应的几种miRNA生物标记。根据其预测的靶基因的基因本体论术语对鉴定出的miRNA的功能进行了研究，表明了细胞过程的调控。我们将结果与先前研究中报道的长非编码RNA（ncRNA）和mRNA的结果进行了比较，此外还发现了先前鉴定的响应于苯刺激而上调或下调的miRNA。我们还观察到，miRNA表达的变化小于长ncRNA和mRNA的变化。综合目前和以前的结果表明，毒性化学刺激物调节miRNA的表达。我们相信使用miRNA（包括由此鉴定的miRNA）作为生物标记物有助于预测特定化学物质的潜在毒性或鉴定暴露于化学危险中的人类个体。