miR-125a Alleviates Inflammatory Damage and Promotes Lipid Synthesis in Bovine Mammary Gland by Targeting IL6R

Bovine mastitis, a major dairy disease, involves inflammation and metabolic dysfunction in mammary epithelial cells (bMECs); however, the regulatory role of microRNAs remains unclear. This study investigated miR-125a in LPS-induced bMECs. miR-125a was downregulated in inflamed bovine mammary tissue and LPS-induced bMECs. Overexpression of miR-125a inhibited pro-inflammatory cytokine release, upregulated proliferation markers, downregulated apoptosis markers, and alleviated oxidative stress. IL6R (interleukin-6 receptor) was identified as a direct target of miR-125a via transcriptome sequencing and dual-luciferase assays. miR-125a suppressed inflammation by targeting IL6R, thereby inhibiting NF-κB pathway activation. Rescue experiments showed miR-125a reversed IL6R-exacerbated inflammation and restored milk fat synthesis-related gene expression and triglyceride accumulation. In vivo mouse experiments confirmed IL6R's pro-inflammatory and milk fat-suppressing effects. Thus, this study elucidates the miR-125a/IL6R/NF-κB axis in coordinately regulating inflammation and milk fat synthesis in bovine mastitis, offering insights for targeted therapy.