miR-206 regulates copper-induced pyroptosis in porcine jejunal epithelial cells by targeting Caspase-1.

Copper (Cu) is an essential trace element in animal organisms, participating in numerous vital processes. However, excessive intake can cause poisonous damage to organs such as the intestines. This study aims to elucidate the role of miR-206 in copper-induced pyroptosis in porcine jejunal epithelial cells and its molecular mechanism. In this study, we found that high-dose copper exposure induces pyroptosis in jejunal epithelial cells, while miR-206 expression was significantly reduced to 0.60 and 0.64 times that of the control group in vivo (Fed a diet containing 250 mg/kg of copper) and in vitro (treatment of IPEC-J2 cells with 400 μM CuSO₄), respectively (P < 0.05). Upregulation of miR-206 significantly reduced the expression of copper-induced pyroptosis-related proteins, with the expression levels of NLRP3, IL-18, and IL-1β downregulated to 0.28-, 0.47-, and 0.42-fold, respectively, compared to the group treated with copper alone (all P < 0.05). At the same time, it markedly alleviated copper-induced cell membrane rupture. Bioinformatics analysis and dual luciferase reporter assays confirmed that Caspase-1 is a direct target of miR-206. Overexpression of Caspase-1 significantly reversed the protective effect of miR-206 against copper-induced pyroptosis, whereas RNA interference of Caspase-1 produced the opposite effect. Therefore, our study reveals the molecular mechanism by which miR-206 alleviates copper-induced pyroptosis in porcine jejunal epithelial cells by suppressing Caspase-1 expression. This provides a novel perspective for investigating the molecular pathology of copper toxicity and lays a theoretical foundation for developing early diagnostic and therapeutic targets for copper toxicity.