Bioinformatics analysis of microRNA and putative target genes in bovine mammary tissue infected with Streptococcus uberis

Abstract

MicroRNA (miRNA) are small single-stranded noncoding RNA with important roles in regulating innate immunity in nonruminants via transcriptional and posttranscriptional mechanisms. Mastitis causes significant losses in the dairy industry and a wealth of large-scale mRNA expression data from mammary tissue have provided fundamental insights into the tissue adaptations to pathogens. We studied the expression of 14 miRNA (miR-10a, -15b, -16a, -17, -21, -31, -145, -146a, -146b, -155, -181a, -205, -221, and -223) associated with regulation of innate immunity and mammary epithelial cell function in tissue challenged with Streptococcus uberis. Those data, along with microarray expression of 2,102 differentially expressed genes, were used for bioinformatics analysis to uncover putative target genes and the most affected biological pathways and functions. Three miRNA (181a, 16, and 31) were downregulated approximately 3- to 5-fold and miR-223 was upregulated approximately 2.5-fold in infected versus healthy tissue. Among differentially expressed genes due to infection, bioinformatics analysis revealed that the studied miRNA share in the regulation of a large number of metabolic (SCD, CD36, GPAM, and FASN), immune/oxidative stress (TNF, IL6, IL10, SOD2, LYZ, and TLR4), and cellular proliferation/differentiation (FOS and CASP4) target genes. This level of complex regulation was underscored by the coordinate effect revealed by bioinformatics on various cellular pathways within the Kyoto Encyclopedia of Genes and Genomes database. Most pathways associated with "cellular processes," "organismal systems," and "diseases" were activated by putative target genes of miR-31 and miR-16a, with an overlapping activation of "immune system" and "signal transduction." A pronounced effect and activation of miR-31 target genes was observed within "folding, sorting, and degradation," "cell growth and death," and "cell communication" pathways, whereas a marked inhibition of "lipid metabolism" occurred. Putative targets of miR-181a had a strong effect on FcγR-mediated phagocytosis, toll-like receptor signaling, and antigen processing and presentation, which were activated during intramammary infections. The targets of both miR-31 and miR-223 had an inhibitory effect on "lipid metabolism." Overall, the combined analyses indicated that changes in mammary tissue immune, metabolic, and cell growth-related signaling pathways during infection might have been mediated in part through effects of miRNA on gene transcription. Differential expression of miRNA supports the view from nonruminant cells/tissues that certain miRNA might be essential for the tissue's adaptive response to infection.

IGF-1 may predict the severity and outcome of patients with sepsis and be associated with microRNA-1 level changes

“…In order to further explore the mechanism of IGF-1 variation in patients with sepsis, miRNA-1 levels were analyzed in patients with sepsis, since IGF-1 is the target gene of miRNA-1 according to previous studies (28,29). The present study demonstrated that patients with sepsis had higher plasma miRNA-1 levels, which was negatively correlated with the IGF-1.…”

Circulating Toll-like receptor 4-responsive microRNA panel in patients with coronary artery disease: results from prospective and randomized study of treatment with renin–angiotensin system blockade

“…Our previous study has already shown an activation of TLR4 signalling pathway and dysregulation of intracellular TLR4-related miRNAs, such as miR-146a/b, in PBMCs obtained from patients with CAD [5]. A number of identified miRNAs, such as miR-146, miR181a, miR-151, miR-31, miR-223, miR-145 and miR-155, are known to regulate various biological pathways including the immune system through the development and function of immune components [30]. It has also been reported that some miRNAs bound as ligands to receptors of the TLR family and thus controlled tumour immune response [31].…”

The Role of microRNAs in Bovine Infection and Immunity

“…Naeem et al examined a panel of 14 miRNAs from mammary tissue biopsied during an in vivo intra-mammary Streptococcus uberis infection (46). Four of the fourteen miRNAs were found to undergo differential expression (Table 1).…”