A miR-19 regulon that controls NF-kappa B signaling

作者：Gantier Michael P; Stunden H James; McCoy Claire E; Behlke Mark A; Wang Die; Kaparakis Liaskos Maria; Sarvestani Soroush T; Yang Yuan H; Xu Dakang; Corr Sinead C; Morand Eric F; Williams Bryan R G^*

来源：Nucleic Acids Research, 2012, 40(16): 8048-8058.

DOI：10.1093/nar/gks521

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-kappa B (NF-kappa B) activity in human and mouse cells. Positive regulation of NF-kappa B signaling by miR-19b involves the coordinated suppression of a regulon of negative regulators of NF-kappa B 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-kappa B signaling, and suggests that targeting this miRNA and linked family members could regulate the activity of NF-kappa B signaling in inflammation.

• 出版日期2012-9
• 单位河北医科大学