miR-183 potentially inhibits NF-κB1 expression by directly targeting its 3'-untranslated region

Nuclear factor-κB (NF-κB) is an important transcription factor. While the NF-κB signaling pathway is modulated by many microRNAs (miRNAs), very few have been reported to target NF-κB1 gene directly. In this study, we used multiple miRNA target prediction programs to predict miRNAs with putative NF-κB1 3'-untranslated region (UTR) binding sites. miR-183 was strongly implicated and experimentally validated by reporter assays. The results showed a reduced expression of the NF-κB1 3'UTR containing luciferase vector by ∼30%, which was comparable to the reduction by miR-9 (the only known miRNA targeting the NF-κB1 3'UTR). Mutagenesis of the miR-183 seed region binding sequence in the NF-κB1 3'UTR abolished the inhibitory effect of miR-183, as noted by the NF-κB1 3'UTR-containing reporter. Moreover, similar to miR-9, miR-183 could down-regulate the expression of the reporter driven by NF-κB promoter to some degree, suggesting that miR-183 might negatively regulate the endogenous NF-κB1. Overall, our data provide computational and experimental evidence that NF-κB1 is a potential target of miR-183.