Zhang Yanmin, Guo Wenrui, Wen Haifeng, Shi Yaqin, Gao Wa, Chen Xindi, Wang Tengyu, Wang Wenlong, Wu Weijie
College of Veterinary Medicine, Inner Mongolia Agricultural University, Inner Mongolia, China.
Inner Mongolia Key Laboratory of Tick-Borne Infectious Diseases, Inner Mongolia, China.
Parasitol Res. 2024 May 30;123(5):226. doi: 10.1007/s00436-024-08238-6.
In this study, 858 novel long non-coding RNAs (lncRNAs) were predicted as sensitive and resistant strains of Haemonchus contortus to ivermectin. These lncRNAs underwent bioinformatic analysis. In total, 205 lncRNAs significantly differed using log2 (difference multiplicity) > 1 or log2 (difference multiplicity) < - 1 and FDR < 0.05 as the threshold for significant difference analysis. We selected five lncRNAs based on significant differences in expression, cis-regulation, and their association with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. These expressions of lncRNAs, namely MSTRG.12610.1, MSTRG.8169.1, MSTRG.6355.1, MSTRG.980.1, and MSTRG.9045.1, were significantly downregulated. These findings were consistent with the results of transcriptomic sequencing. We further investigated the relative expression of target gene mRNAs and the regulation of mRNA and miRNA, starting with lncRNA cis-regulation of mRNA, and constructed a lncRNA-mRNA-miRNA network regulation. After a series of statistical analyses, we finally screened out UGT8, Unc-116, Fer-related kinase-1, GGPP synthase 1, and sart3, which may be involved in developing drug resistance under the regulation of their corresponding lncRNAs. The findings of this study provide a novel direction for future studies on drug resistance targets.
在本研究中，858 个新型长链非编码 RNA（lncRNAs）被预测为捻转血矛线虫对伊维菌素的敏感和耐药菌株。这些 lncRNAs 进行了生物信息学分析。总共，以 log2（差异倍数）>1 或 log2（差异倍数）<-1 以及 FDR<0.05 作为显著差异分析的阈值，有 205 个 lncRNAs 存在显著差异。我们基于表达的显著差异、顺式调控以及它们与基因本体论和京都基因与基因组百科全书途径的关联，选择了 5 个 lncRNAs。这些 lncRNAs，即 MSTRG.12610.1、MSTRG.8169.1、MSTRG.6355.1、MSTRG.980.1 和 MSTRG.9045.1 的表达显著下调。这些发现与转录组测序结果一致。我们从 lncRNA 对 mRNA 的顺式调控入手，进一步研究了靶基因 mRNA 的相对表达以及 mRNA 和 miRNA 的调控，并构建了 lncRNA-mRNA-miRNA 网络调控。经过一系列统计分析，我们最终筛选出了 UGT8、Unc-116、铁相关激酶-1、GGPP 合酶 1 和 sart3，它们可能在其相应 lncRNAs 的调控下参与耐药性的产生。本研究结果为未来耐药靶点的研究提供了新的方向。
