Zhao Yunli, Wu Qiuli, Li Yiping, Nouara Abdelli, Jia Ruhan, Wang Dayong
Key Laboratory of Environmental Medicine Engineering in Ministry of Education, Medical School of Southeast University, Nanjing 210009, China.
Nanoscale. 2014 Apr 21;6(8):4275-84. doi: 10.1039/c3nr06784j. Epub 2014 Mar 10.
We employed an in vivo Caenorhabditis elegans assay system to perform SOLiD sequencing analysis to identify the possible microRNA (miRNA) targets of multi-walled carbon nanotubes (MWCNTs). Bioinformatics analysis on targeted genes for the identified dysregulated miRNAs in MWCNT exposed nematodes demonstrates their involvement in many aspects of biological processes. We used loss-of-function mutants for the identified dysregulated miRNAs to perform toxicity assessment by evaluating functions of primary and secondary targeted organs, and found the miRNA mutants with susceptible or resistant property towards MWCNT toxicity. Both the physiological state of the intestine and defecation behavior were involved in the control of the susceptible or resistant property occurrence for specific miRNA mutants towards MWCNT toxicity. This work provides the molecular basis at the miRNA level for future chemical design to reduce the nanotoxicity of MWCNTs and further elucidation of the related toxicological mechanism.
我们采用了一种体内秀丽隐杆线虫检测系统来进行SOLiD测序分析，以确定多壁碳纳米管（MWCNT）可能的微小RNA（miRNA）靶标。对MWCNT暴露线虫中鉴定出的失调miRNA的靶向基因进行生物信息学分析，表明它们参与了生物过程的许多方面。我们使用鉴定出的失调miRNA的功能缺失突变体，通过评估初级和次级靶器官的功能来进行毒性评估，发现了对MWCNT毒性具有敏感或抗性的miRNA突变体。肠道的生理状态和排便行为都参与了特定miRNA突变体对MWCNT毒性的敏感或抗性特性的控制。这项工作为未来的化学设计提供了miRNA水平的分子基础，以降低MWCNT的纳米毒性并进一步阐明相关的毒理学机制。
