Serum miR-128 as a potential biomarker for asthma in horses

MicroRNAs regulate post-transcriptional gene expression and can be exported from the cells in exosomes or bound to RNA-binding proteins. Circulating microRNAs in body fluids may act in a hormone-like manner and play important roles in disease initiation and progression. Hence, these microRNAs are promising candidates as biomarkers for many diseases. We aimed to identify serum microRNA biomarkers in the equine model of asthma. Small RNA derived from the serum of 35 control and 37 asthmatic horses was used for next generation sequencing and further differential expression analysis. We then retrieved gene targets of the most significantly deregulated miRNA and investigated their differential expression in peripheral blood mononuclear cells (PBMCs) derived from the same blood collection as the serum samples used in this study. We identified significant differences in the expression of four miRNAs between case and control horses: eca-miR-128, eca-miR-744, and two homologs eca-miR-107a and eca-miR-103. The most significantly deregulated eca-miR-128 and eca-miR-744 were additionally affected by the level of haemolysis. Interestingly, miR-128 is known to affect T cell differentiation by negatively affecting Th1 maturation, while promoting Th2 and Th17 maturation. Hence, we propose a Th2/Th17 type immune response to underlie the pathophysiology of equine asthma. Thirty potential target genes of miR-128 were previously reported as differentially expressed in unstimulated or antigen stimulated PBMCs. The three upregulated genes in unstimulated cells (RAB20, BAZ2B, and HLX) were previously reported to be associated with asthma-like conditions in humans. We propose the miR-128 as a potential new biomarker for asthma in horses.