Abstract：
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.
摘要：
在这项研究中,858个新的长链非编码RNA（lncRNAs）被预测为对伊维菌素的敏感和抗性菌株。这些lncRNAs进行了生物信息学分析。总的来说,使用log2(差异多重性)>1或log2(差异多重性)<-1和FDR<0.05作为显著差异分析的阈值,205个lncRNA显著不同。我们基于表达的显著差异选择了五个lncRNAs，顺式监管，以及它们与基因本体论和京都百科全书的基因和基因组途径的关联。这些lncRNAs的表达，即MSTRG.12610.1、MSTRG.8169.1、MSTRG.635.1、MSTRG.90.1和MSTRG.9045.1显著下调。这些发现与转录组测序的结果一致。我们进一步研究了靶基因mRNA的相对表达以及mRNA和miRNA的调控,从mRNA的lncRNA顺式调节开始，并构建了一个lncRNA-mRNA-miRNA网络调控。经过一系列的统计分析,我们最终筛选出UGT8，Unc-116，Fer相关激酶-1，G3GPP合酶1和sart3，它们可能参与在其相应的lncRNAs的调节下发展耐药性。本研究结果为今后的耐药靶点研究提供了新的方向。
