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宿主 miR-101b-3p 通过超氧化物歧化酶 3 对广州血管圆线虫寄生的调控作用。

Regulatory effect of host miR-101b-3p on parasitism of nematode Angiostrongylus cantonensis via superoxide dismutase 3.

机构信息

College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.

Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory for Tropical Diseases Control (SYSU), Ministry of Education, Guangzhou 510080, China; Provincial Engineering Technology Research Center for Diseases-vectors Control, Guangdong, Guangzhou 510080, China; Institute of Virology, Technical University of Munich/Helmholtz Zentrum München, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany.

出版信息

Biochim Biophys Acta Gene Regul Mech. 2019 May;1862(5):557-566. doi: 10.1016/j.bbagrm.2019.02.004. Epub 2019 Feb 11.

Abstract

MicroRNA plays a vital role in the regulation of host-parasite interaction. In recent years, genomic and transcriptomic resources have become increasingly available for many helminths, but only a limited number of reports in this area are on the regulatory effects of host microRNAs on parasitic nematodes. In this work, we screened increased expression of host microRNAs after nematode infection from miRNA-seq data and predicted target genes by combined bioinformatics analysis and transcriptional profiling. We elucidated regulatory effects of one host miRNA on nematode infection using miRNA inhibitor and adeno-associated virus (AAV)-based TuD miRNA inhibitor. Using AAV-based TuD miRNA inhibitor, we showed that stable blockade of mmu-miR-101b-3p could alleviate the pathological damages of Angiostrongylus cantonensis, a parasitic nematode. Data from a luciferase report assay showed that mmu-miR-101b-3p targeted the extracellular superoxide dismutase 3 (Acsod3). Increased Acsod3 expression in larvae and alleviated oxidative damages were seen in the groups receiving mmu-miR-101b-3p inhibitor treatment in vitro and AAV-based TuD miRNA inhibitor injection in vivo. Results of this study demonstrate that murine miR-101b-3p inhibits the expression of antioxidant enzyme in A. cantonensis to strengthen host oxidative responses to nematodes. This work expands our knowledge of interspecies regulation of nematode gene expression by of host miRNAs.

摘要

微小 RNA 在宿主-寄生虫相互作用的调控中起着至关重要的作用。近年来,许多寄生虫的基因组和转录组资源变得越来越丰富,但在这个领域仅有少数关于宿主 microRNAs 对寄生线虫的调控作用的报道。在这项工作中,我们从 miRNA-seq 数据中筛选了感染线虫后宿主 microRNAs 的表达上调,并通过综合生物信息学分析和转录谱分析预测了靶基因。我们使用 miRNA 抑制剂和基于腺相关病毒 (AAV) 的 TuD miRNA 抑制剂阐明了一种宿主 miRNA 对线虫感染的调控作用。使用基于 AAV 的 TuD miRNA 抑制剂,我们表明稳定阻断 mmu-miR-101b-3p 可以减轻寄生线虫广州管圆线虫的病理损伤。荧光素酶报告试验结果表明,mmu-miR-101b-3p 靶向细胞外超氧化物歧化酶 3 (Acsod3)。在体外接受 mmu-miR-101b-3p 抑制剂处理和体内接受 AAV 基于 TuD miRNA 抑制剂注射的幼虫中,Acsod3 表达增加,氧化损伤减轻。这项研究的结果表明,鼠 miR-101b-3p 抑制了 A. cantonensis 中抗氧化酶的表达,从而增强了宿主对线虫的氧化反应。这项工作扩展了我们对宿主 microRNAs 调控线虫基因表达的种间调节的认识。

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