| First Author | Gantier MP | Year | 2012 |
| Journal | Nucleic Acids Res | Volume | 40 |
| Issue | 16 | Pages | 8048-58 |
| PubMed ID | 22684508 | Mgi Jnum | J:198890 |
| Mgi Id | MGI:5499703 | Doi | 10.1093/nar/gks521 |
| Citation | Gantier MP, et al. (2012) A miR-19 regulon that controls NF-kappaB signaling. Nucleic Acids Res 40(16):8048-58 |
| abstractText | Fine-tuning of inflammatory responses by microRNAs (miRNAs) is complex, as they can both enhance and repress expression of pro-inflammatory mediators. In this study, we investigate inflammatory responses following global miRNA depletion, to better define the overall contribution of miRNAs to inflammation. We demonstrate that miRNAs positively regulate Toll-like receptor signaling using inducible Dicer1 deletion and global miRNA depletion. We establish an important contribution of miR-19b in this effect, which potentiates nuclear factor-kappaB (NF-kappaB) activity in human and mouse cells. Positive regulation of NF-kappaB signaling by miR-19b involves the coordinated suppression of a regulon of negative regulators of NF-kappaB signaling (including A20/Tnfaip3, Rnf11, Fbxl11/Kdm2a and Zbtb16). Transfection of miR-19b mimics exacerbated the inflammatory activation of rheumatoid arthritis primary fibroblast-like synoviocytes, demonstrating its physiological importance in the pathology of this disease. This study constitutes, to our knowledge, the first description of a miR-19 regulon that controls NF-kappaB signaling, and suggests that targeting this miRNA and linked family members could regulate the activity of NF-kappaB signaling in inflammation. |
