MicroRNA-22 and microRNA-140 suppress NF-κB activity by regulating the expression of NF-κB coactivators

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Japan.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 08/2011; 411(4):826-31. DOI: 10.1016/j.bbrc.2011.07.048
Source: PubMed


Nuclear factor κB (NF-κB) is a transcription factor that regulates a set of genes that are critical to many biological phenomena, including liver tumorigenesis. To identify microRNAs (miRNAs) that regulate NF-κB activity in the liver, we screened 60 miRNAs expressed in hepatocytes for their ability to modulate NF-κB activity. We found that miRNA-22 and miRNA-140-3p significantly suppressed NF-κB activity by regulating the expression of nuclear receptor coactivator 1 (NCOA1) and nuclear receptor-interacting protein 1 (NRIP1), both of which are NF-κB coactivators. Our results provide new information about the roles of miRNAs in the regulation of NF-κB activity.

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    • "Although both miR-140-5p and -3p are transcribed from the same precursor transcript pre-miR-140, they have different seed sequences and are, therefore, predicted to target different genes. While miR-140-5p was shown to target several genes involved in OA, miR-140-3p has been reported to target dynamin 1, which plays a role in the central nervous system [16] and the nuclear factor kappa B (NF-κB) co-activator nuclear receptor-interacting protein 1 [17]. "
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    • "Because upregulation of MICA expression was observed in Dicer-knockdown cells18, we hypothesized that MICA expression levels may be at least partly regulated by miRNAs. We initially tested miRNAs that might affect MICA expression using reporter constructs into which MICA 3′-untranslated region (3′UTR) sequences were cloned and by transiently overexpressing 76 mature synthetic microRNAs, which were selected on the basis of their hepatic expression level, as in our previous studies1920. Among the microRNAs examined, several may target MICA 3′UTR (Supplementary Figure 1). "
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    Scientific Reports 09/2013; 3:2739. DOI:10.1038/srep02739 · 5.58 Impact Factor
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    • "Plasmids expressing miR122 and miR185 precursors and the corresponding firefly luciferase-based reporters have been described previously835. Plasmids expressing miRNA-103 precursors and the corresponding luciferase reporter were newly constructed according to protocols reported previously8. "
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