Computational Network Analysis Identifies Evolutionarily Conserved miRNA Gene Interactions Potentially Regulating Immune Response in Bovine Trypanosomosis

Abstract

Bovine trypanosomosis is a devastating disease that causes huge economic loss to the global cattle industry on a yearly basis. Selection of accurate biomarkers are important in early disease diagnosis and treatment. Of late, micro-RNAs (miRNAs) are becoming the most useful biomarkers for both infectious and non-infectious diseases in humans, but this is not the case in animals. miRNAs are non-coding RNAs that regulate gene expression through binding to the 3′-, 5′-untranslated regions (UTR) or coding sequence (CDS) region of one or more target genes. The molecular identification of miRNAs that regulates the expression of immune genes responding to bovine trypanosomosis is poorly defined, as is the possibility that these miRNAs could serve as potential biomarkers for disease diagnosis and treatment currently unknown. To this end, we utilized in silico tools to elucidate conserved miRNAs regulating immune response genes during infection, in addition to cataloging significant genes. Based on the p value of 1.77E-32, we selected 25 significantly expressed immune genes. Using prediction analysis, we identified a total of 4,251 bovine miRNAs targeting these selected genes across the 3′UTR, 5′UTR and CDS regions. Thereafter, we identified candidate miRNAs based on the number of gene targets and their abundance at the three regions. In all, we found the top 13 miRNAs that are significantly conserved targeting 7 innate immune response genes, including bta-mir-2460, bta-mir-193a, bta-mir-2316, and bta-mir-2456. Our gene ontology analysis suggests that these miRNAs are involved in gene silencing, cellular protein modification process, RNA-induced silencing complex, regulation of humoral immune response mediated by circulating immunoglobulin and negative regulation of chronic inflammatory response, among others. In conclusion, this study identifies specific miRNAs that may be involved in the regulation of gene expression during bovine trypanosomosis. These miRNAs have the potential to be used as biomarkers in the animal and veterinary research community to facilitate the development of tools for early disease diagnosis/detection, drug targeting, and the rational design of drugs to facilitate disease treatment.

SNP Diversity in CD14 Gene Promoter Suggests Adaptation Footprints in Trypanosome Tolerant N’Dama (Bos taurus) but not in Susceptible White Fulani (Bos indicus) Cattle

“…We confirmed the identified miRNAs with two other prediction algorithms and databases; miRBase [30] and TargetScan [31]. We selected candidate miRNAs from these databases to analyze further, as previously described [25,26].…”

“…Forward and reverse sequences from N'Dama and White Fulani were individually processed, assembled, and contigs were made with SeqMan Pro of the Lasergene program, version 4.0 (DNAStar, Madison WI, USA). The contigs from both breeds were individually used to search the bovine genome ARS-UCD1.2 assembly [26] (Figure 1). gene ontology database with each miRNA to ascertain relevant biological processes.…”

“…We have utilized qualitative data on CD14 gene promoter to decipher immune response and susceptibility to malaria infection [18], showing a defective response by mutant variants, driving a cascade that worsens disease and multiple deleterious outcomes [22][23][24]. In addition, we have also shown that there are evolutionarily conserved microRNAs involved in the CD14-mediated immune response during bovine trypanosomosis [25], demonstrating their significance in regulating gene expression [26]. Hence, there is a need to identify and characterize naturally occurring variations within the bovine CD14 promoter of cattle breeds that may be associated with disease tolerance or susceptibility.…”

Integrative Network Analysis of Predicted miRNA-Targets Regulating Expression of Immune Response Genes in Bovine Coronavirus Infection

“…They have been studied as a treatment for atherosclerosis, hepatitis C virus, and cancers (Scheel et al, 2017). Additionally, miRNA have been demonstrated to have significant implications in bovine disease elucidation, including immune response to viral infection (Vidigal and Ventura, 2015;Scheel et al, 2017;Morenikeji et al, 2019).…”

“…This study aims to elucidate the role of miRNAs in the host immune response to BCoV, demonstrate miRNA-target interactions, identify potential markers for disease diagnosis, and possible therapeutic drug targets. Figure 1A shows the pipeline we utilized for this study, including a step by step flowchart starting from literature search to miRNA variant identification, as previously described (Morenikeji et al, 2019). To begin, we searched for recently published, publicly available literature, pertaining to gene expression, and particularly bovine coronavirus from biomedical science repository PubMed and Google Scholar.…”