title: miR-183 potentially inhibits NF-κB1 expression by directly targeting its 3'-untranslated region.
abstract: 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.
authors.affiliation: Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-Sen University, Guangzhou 510080, China Key Laboratory of Tropical Disease Control, Sun Yat-Sen University, Ministry of Education, Guangzhou 510080, China.
authors.forename: Fushen
authors.initials: F
authors.lastname: Sha
authors.affiliation: Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-Sen University, Guangzhou 510080, China Key Laboratory of Tropical Disease Control, Sun Yat-Sen University, Ministry of Education, Guangzhou 510080, China.
authors.forename: Shuangxing
authors.initials: S
authors.lastname: Wu
authors.affiliation: Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-Sen University, Guangzhou 510080, China Key Laboratory of Tropical Disease Control, Sun Yat-Sen University, Ministry of Education, Guangzhou 510080, China xmguo2005@yahoo.com zhangh92@mail.sysu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Zhongshan School of Medicine, Institute of Human Virology, Sun Yat-Sen University, Guangzhou 510080, China Key Laboratory of Tropical Disease Control, Sun Yat-Sen University, Ministry of Education, Guangzhou 510080, China Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China xmguo2005@yahoo.com zhangh92@mail.sysu.edu.cn.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Guo
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015536:Down-Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D012984:Software
chemical_list: D020413:3' Untranslated Regions; C533449:MIRN183 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D052002:NF-kappa B p50 Subunit; D008156:Luciferases
keywords: NF-κB1; computational prediction; microRNA; reporter assay