circRNA-miRNA interactions regulate the immune response by activating the NF-κB pathway through targeting IκBα in...

Non-coding RNAs (ncRNAs) play crucial regulatory roles in the NF-κB signaling pathway in fish. IκB (inhibitor of kappa B) acts as a key inhibitor of NF-κB. In our study on black rockfish (Sebastes schlegelii), we identified two paralogous copies of the IκBα gene, designated IκBα1 and IκBα2. Phylogenetic analysis confirmed that IκBα1 and IκBα2 represent teleost paralogs. Consequently, we investigated the interactions of these two IκBα paralogs with the NF-κB signaling pathway and their post-transcriptional regulation in S. schlegelii. Furthermore, expression levels of miR-286 and miR-786, which target IκBα1 and IκBα2 respectively, were significantly elevated in groups infected with Edwardsiella piscicida or Streptococcus iniae, and in those treated with LPS or poly(I:C). This suggests their involvement in teleost antibacterial and antiviral responses. Our findings indicate that miR-286 and miR-786 may activate the NF-κB signaling pathway by suppressing IκBα1 and IκBα2 expression, respectively, thereby inducing inflammatory responses. Concurrently, we demonstrated that circRNA-4254 and circRNA-273 bind to miR-286 and miR-786, respectively. We validated the mechanism through which these ncRNAs regulate innate immune responses at both gene and protein levels. This elucidates post-transcriptional regulation during immune responses in S. schlegelii and provides a theoretical foundation for developing disease control strategies in this species.