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吡喹酮处理猪带绦虫囊尾蚴的 microRNA 分析和猪带绦虫 microRNA 的全基因组鉴定。

microRNA analysis of Taenia crassiceps cysticerci under praziquantel treatment and genome-wide identification of Taenia solium miRNAs.

机构信息

Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires (UBA), Paraguay 2155, Piso 13, Buenos Aires, Argentina.

Instituto de Biotecnología, CICVyA-INTA, Dr. N. Repetto y Los Reseros s/n, 1686 Hurlingham, Buenos Aires, Argentina.

出版信息

Int J Parasitol. 2017 Sep;47(10-11):643-653. doi: 10.1016/j.ijpara.2017.04.002. Epub 2017 May 17.

DOI:10.1016/j.ijpara.2017.04.002
PMID:28526608
Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that have emerged as important regulators of gene expression and perform critical functions in development and disease. In spite of the increased interest in miRNAs from helminth parasites, no information is available on miRNAs from Taenia solium, the causative agent of cysticercosis, a neglected disease affecting millions of people worldwide. Here we performed a comprehensive analysis of miRNAs from Taenia crassiceps, a laboratory model for T. solium studies, and identified miRNAs in the T. solium genome. Moreover, we analysed the effect of praziquantel, one of the two main drugs used for cysticercosis treatment, on the miRNA expression profile of T. crassiceps cysticerci. Using small RNA-seq and two independent algorithms for miRNA prediction, as well as northern blot validation, we found transcriptional evidence of 39 miRNA loci in T. crassiceps. Since miRNAs were mapped to the T. solium genome, these miRNAs are considered common to both parasites. The miRNA expression profile of T. crassiceps was biased to the same set of highly expressed miRNAs reported in other cestodes. We found a significant altered expression of miR-7b under praziquantel treatment. In addition, we searched for miRNAs predicted to target genes related to drug response. We performed a detailed target prediction for miR-7b and found genes related to drug action. We report an initial approach to study the effect of sub-lethal drug treatment on miRNA expression in a cestode parasite, which provides a platform for further studies of miRNA involvement in drug effects. The results of our work could be applied to drug development and provide basic knowledge of cysticercosis and other neglected helminth infections.

摘要

微小 RNA(miRNAs)是一类小的非编码 RNA,它们作为基因表达的重要调控因子发挥作用,在发育和疾病中发挥关键功能。尽管人们对寄生虫的 miRNAs 越来越感兴趣,但关于引起囊虫病(一种影响全球数百万人的被忽视疾病)的绦虫 Taenia solium 的 miRNAs 却没有信息。在这里,我们对 Taenia crassiceps 的 miRNAs 进行了全面分析,Taenia crassiceps 是 T. solium 研究的实验室模型,并鉴定了 T. solium 基因组中的 miRNAs。此外,我们分析了吡喹酮(用于囊虫病治疗的两种主要药物之一)对 T. crassiceps 囊尾蚴 miRNA 表达谱的影响。使用小 RNA-seq 和两种用于 miRNA 预测的独立算法以及 northern blot 验证,我们在 T. crassiceps 中发现了 39 个 miRNA 基因座的转录证据。由于 miRNA 被映射到 T. solium 基因组上,因此这些 miRNA 被认为是两种寄生虫共有的。T. crassiceps 的 miRNA 表达谱偏向于其他绦虫中报道的高度表达 miRNA。我们发现 miR-7b 在吡喹酮处理下表达显著改变。此外,我们还搜索了预测靶向与药物反应相关基因的 miRNA。我们对 miR-7b 进行了详细的靶基因预测,并找到了与药物作用相关的基因。我们报告了一种在绦虫寄生虫中研究亚致死药物处理对 miRNA 表达影响的初步方法,为进一步研究 miRNA 参与药物作用提供了平台。我们工作的结果可应用于药物开发,并为囊虫病和其他被忽视的蠕虫感染提供基础知识。

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