综合分析转录组图谱和 lncRNA-miRNA-mRNA 竞争性内源性 RNA 调控网络,确定奶牛约翰氏病相关基因和途径的生物功能效应。

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Farzad Ghafouri, Vahid Dehghanian Reyhan, Mostafa Sadeghi, Seyed Reza Miraei-Ashtiani, John P Kastelic, Herman W Barkema, Masoud Shirali
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引用次数: 0

摘要

副结核病或约翰氏病(JD)是由副结核分枝杆菌(MAP)引起的一种慢性肉芽肿性肠胃炎,给全世界的奶牛群造成了巨大的经济损失并降低了动物福利。目前,乳牛对 MAP 感染的免疫反应所涉及的分子机制和生物功能尚不清楚。我们的目的是整合转录组图谱和竞争性内源性 RNA(ceRNA)网络分析,以确定参与奶牛外周血单核细胞(PBMC)对 MAP 感染的分子调控的关键信使 RNA(mRNA)和调控 RNA。通过整合基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,我们共鉴定出 28 个 lncRNA、42 个 miRNA 和 370 个 mRNA。在这方面,我们确定了 21 个参与 MAP 感染的中心基因(CCL20、CCL5、CD40、CSF2、CXCL8、EIF2AK2、FOS、IL10、IL17A、IL1A、IL1B、IRF1、MX2、NFKB1、NFKBIA、PTGS2、SOCS3、TLR4、TNF、TNFAIP3 和 VCAM1)。此外,通过聚类分析还发现了8个候选子网,包括8个lncRNA、29个miRNA和237个mRNA,而对鉴定出的RNA进行的GO富集分析则发现,在生物过程、分子功能和细胞组分类别中,分别有510、22和11个与MAP感染相关的GO术语被显著富集。被富集的与 MAP 感染有关的主要代谢-信号通路包括免疫系统过程、防御反应、对细胞因子的反应、白细胞迁移、T 细胞活化调节、对细菌的防御反应、NOD 样受体、B 细胞受体、TNF、NF-kappa B、IL-17 和 T 细胞受体信号通路。MAP 阳性样本组和 MAP 阴性样本组的转录组图谱,加上 JD 致病性强度表型差异背后的 ceRNA 调控网络,为乳牛对 MAP 感染的免疫系统反应的分子机制提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Integrated Analysis of Transcriptome Profiles and lncRNA-miRNA-mRNA Competing Endogenous RNA Regulatory Network to Identify Biological Functional Effects of Genes and Pathways Associated with Johne's Disease in Dairy Cattle.

Paratuberculosis or Johne's disease (JD), a chronic granulomatous gastroenteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP), causes huge economic losses and reduces animal welfare in dairy cattle herds worldwide. At present, molecular mechanisms and biological functions involved in immune responses to MAP infection of dairy cattle are not clearly understood. Our purpose was to integrate transcriptomic profiles and competing endogenous RNA (ceRNA) network analyses to identify key messenger RNAs (mRNAs) and regulatory RNAs involved in molecular regulation of peripheral blood mononuclear cells (PBMCs) for MAP infection in dairy cattle. In total, 28 lncRNAs, 42 miRNAs, and 370 mRNAs were identified by integrating gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In this regard, we identified 21 hub genes (CCL20, CCL5, CD40, CSF2, CXCL8, EIF2AK2, FOS, IL10, IL17A, IL1A, IL1B, IRF1, MX2, NFKB1, NFKBIA, PTGS2, SOCS3, TLR4, TNF, TNFAIP3, and VCAM1) involved in MAP infection. Furthermore, eight candidate subnets with eight lncRNAs, 29 miRNAs, and 237 mRNAs were detected through clustering analyses, whereas GO enrichment analysis of identified RNAs revealed 510, 22, and 11 significantly enriched GO terms related to MAP infection in biological process, molecular function, and cellular component categories, respectively. The main metabolic-signaling pathways related to MAP infection that were enriched included the immune system process, defense response, response to cytokine, leukocyte migration, regulation of T cell activation, defense response to bacterium, NOD-like receptor, B cell receptor, TNF, NF-kappa B, IL-17, and T cell receptor signaling pathways. Contributions of transcriptome profiles from MAP-positive and MAP-negative sample groups plus a ceRNA regulatory network underlying phenotypic differences in the intensity of pathogenicity of JD provided novel insights into molecular mechanisms associated with immune system responses to MAP infection in dairy cattle.

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来源期刊
Non-Coding RNA
Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
6.70
自引率
4.70%
发文量
74
审稿时长
10 weeks
期刊介绍: Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.
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