Identification of RNA biomarkers for chemical safety screening

Although it is not yet possible to replace in vivo animal testing completely, the need for a more efficient method for toxicity testing, such as an in vitro cell-based assay, has been widely acknowledged. Previous studies have focused on mRNAs as biomarkers; however, recent studies have revealed that non-coding RNAs (ncRNAs) are also efficient novel biomarkers for toxicity testing. Here, we used deep sequencing analysis (RNA-seq) to identify novel RNA biomarkers, including ncRNAs. We used undifferentiated mouse embryonic stem cells (mESCs) as a simplified cell-based toxicity assay. RNA-seq revealed that many mRNAs and ncRNAs responded substantially to the chemical compounds in mESCs. This finding indicates that ncRNAs can be used as novel RNA biomarkers for chemical safety screening.

尽管目前尚无法完全替代体内动物实验，但学界已普遍认可开发更高效的毒性检测方法（如体外细胞检测实验）的必要性。此前的研究多以信使RNA（messenger RNA, mRNA）作为生物标志物；然而近期研究表明，非编码RNA（non-coding RNAs, ncRNAs）同样可作为毒性检测的高效新型生物标志物。本研究采用深度测序分析（RNA-seq）技术，以识别包括非编码RNA在内的新型RNA生物标志物。研究选用未分化小鼠胚胎干细胞（mouse embryonic stem cells, mESCs）作为简化的细胞毒性检测体系。RNA-seq分析结果显示，在该细胞体系中，大量信使RNA与非编码RNA均对受试化学化合物产生了显著响应。该发现表明，非编码RNA可作为化学物质安全筛查的新型RNA生物标志物。