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- W3170428762 abstract "Abstract Background: Bovine mastitis is a mammary gland infectious disease caused by a variety of pathogens with a devasting economic impact worldwide. Pre- and post-transcriptional modifications, including transcription factors (TFs), altering gene expression are emerging foci of disease studies, with minimal studies revealing the importance of non-coding transcripts, like long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). We hypothesize TFs, lncRNAs and miRNAs can modulate the immune response in bovine mastitis and can potentially serve as disease biomarkers and/or drug targets. Methods: With computational analyses, we aimed to identify candidate bovine mastitis genes and construct the networks of miRNA, lncRNA and TFs regulating the gene’s mRNA, affecting disease pathogenesis. Experimentally validated genes associated with bovine mastitis were obtained through an extensive search for significantly mentioned genes, utilizing several databases. Prediction of miRNA and lncRNA binding bovine mastitis candidate genes were performed through several algorithms and software that relied on base pair complementation, evolutionary conservation, and thermodynamic stability of binding regions. Combined interactome network of lncRNAs, miRNAs, TFs and immune gene targets were constructed. Results: Sixteen of 923 genes were found to be highly significant in bovine mastitis disease pathway including, CD4, IL-10, IFNγ, IL-4, TLR4, TNFα, and CD14. Remarkably, we found six miRNAs, two being bta-miR-223 and bta-miR-24-3p, to bind to several targets. Eight out of 22 lncRNA, such as NONBTAT027932.1 and XR_003029725.1, were identified as regulatory elements that target the genes based on the normalized binding free energies ranging from -0.1774 to -2.875. Similarly identified were 17 TFs, including JUN and CREB. Our functional and pathway analyses revealed several pathways like lipopolysaccharide-mediated signaling pathway, regulation of chemokine (C-X-C motif) ligand 2 production and regulation of IL-23 production among others. Conclusions: The overarching interactome in this study is the first of its kind regarding bovine mastitis, deserving further in vitro/in vivo explication for specific molecular regulatory mechanisms during bovine mastitis immune response, which could lay the foundation for development of disease markers and therapeutic intervention." @default.
- W3170428762 created "2021-06-22" @default.
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- W3170428762 date "2021-04-26" @default.
- W3170428762 modified "2023-10-18" @default.
- W3170428762 title "Regulatory Network of MiRNAs, IncRNAs, Transcription Factors and Target Genes Associated With Immune Response in Bovine Mastitis" @default.
- W3170428762 doi "https://doi.org/10.21203/rs.3.rs-434766/v1" @default.
- W3170428762 hasPublicationYear "2021" @default.
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