Regulatory network of miRNAs, lncRNAs and target genes associated with immune response in bovine mastitis

Abstract

Bovine mastitis is mainly caused by Escherichia coli and Streptococcus uberis. It is associated with complex multifactorial phenotypes, requiring an integrative approach to elucidate the molecular networks underlying variable disease outcome. The association of lncRNAs, miRNAs and their target as key players in immunity regulation has not been studied in bovine mastitis. We hypothesize that non-coding genes could mediate immune response in bovine mastitis and have potential as disease markers or drug targets. Through bioinformatic analyses, we investigated the networks of lncRNAs, miRNAs and mRNAs, and identified key regulatory elements driving immune response in bovine mastitis. Our analyses reveal 16 highly significant immune response genes including MYD88, IL-10, IL-4, ICAM1, CXCL8, IL-18 and CSF2. Notably, of the 2904 miRNAs reported, six - bta-miR-24-3p, bta-miR-149-5p, bta-miR-223, bta-miR-185, bta-miR-328, and bta-miR-874, were predicted to bind multiple regions of target genes. Likewise, eight out of 22 lncRNAs including NONBTAT001181.2, XR_003030515.1 and XR_003030515.1 bind 13 mRNA targets. Of interest, some of these are conserved in 15 different species, including Homo sapiens. Our functional analyses show that these lncRNAs and miRNAs may regulate pathogenesis of bovine mastitis through lipopolysaccharide-mediated signaling pathway, regulation of chemokine (C-X-C motif) ligand 2 production, regulation of IL-23 production, positive regulation of chemokine production and pattern recognition receptor activity. This interactome lays a foundation for molecular interconnectivity of regulatory elements in bovine mastitis, deserving further elucidation for potential vaccine and therapeutics.