miR-122 regulates the JAK-STAT signalling pathway by down-regulating <i>EPO</i> in the mammary gland during <i>Streptococcus agalactiae</i>-induced mastitis

MicroRNA (miRNA) are single-stranded non-coding RNA of approximately 22 nucleotides estimated to regulate 60% of human and animal genes some of which are associated with cell differentiation, signal transduction and immune processes. <i>Streptococcus agalactiae</i> (<i>S. agalactiae</i>)-induced bovine mastitis is associated with up-regulation of miR-122 and down-regulation of erythropoietin (<i>EPO</i>) abundance in mammary gland tissue. TargetScan analysis revealed that <i>EPO</i> is a predicted target gene of miR-122 and this regulatory relationship was verified by dual-luciferase reporter assay. Overexpression of miR-122 in primary bovine mammary cells led to down-regulation of <i>EPO</i> and also the JAK-STAT signalling pathway genes <i>EPOR</i>, <i>JAK2</i>, <i>STAT5A</i> and <i>STAT5B</i>. Accordingly, the mRNA abundance of <i>BCL-2</i>, a downstream gene in the JAK-STAT signalling pathway was significantly down-regulated. Under conditions of miR-122 inhibition, <i>EPO</i>, <i>EPOR</i>, <i>JAK2</i>, <i>STAT5A</i> and <i>STAT5B</i> were up-regulated. These results demonstrated that, through its action on <i>EPO</i>, miR-122 may play an important role in <i>S. agalactiae</i>-induced mastitis by regulating the JAK-STAT signalling pathway.HighlightsUnderstanding the relationship among miR-122, <i>EPO</i> and the JAK-STAT pathway would be helpful in developing new strategies for controlling mastitis. Understanding the relationship among miR-122, <i>EPO</i> and the JAK-STAT pathway would be helpful in developing new strategies for controlling mastitis.