Aryl Hydrocarbon Receptor-Dependent miRNA-382–5p Mediates the Classical Pyroptosis Induced by Foodborne Benzo(a)pyrene through Targeting IκB in Liver

Benzo(a)pyrene (BaP), a carcinogen prevalent in high-temperature processed foods, activates the aryl hydrocarbon receptor (AhR) and induces liver pyroptotic injury. MicroRNAs regulate mRNA expression and are involved in BaP toxicity. In this study, we investigated the essential role of microRNA in BaP-induced pyroptosis. <i>In vivo</i>, BaP induces liver pyroptotic injury by activating AhR, which may be attributed to AhR's influence on microRNA expression. The miRNA-382-5p/Akt and miRNA-382-5p/IκB pairs were predicted to post-transcriptionally regulate pyroptosis. <i>In vitro</i>, miRNA-382-5p activates the classical NF-κB/NLRP3/Caspase-1 pyroptosis signaling pathway by targeting and inhibiting the IκB gene. Furthermore, AhR activation by BaP could promote the high expression of miRNA-382-5p, thereby upregulating the NF-κB/NLRP3/Caspase-1 pyroptosis signaling pathway. In summary, we established that the AhR-mediated miR-382-5p/NF-κB/NLRP3/Caspase-1 axis is a key driver of BaP-induced pyroptosis in hepatocytes and elucidated the underlying mechanisms. These findings provide a valuable theoretical basis for considering miRNA-382-5p as a potential target for preventing BaP toxicity.