Int J Biol Sci 2015; 11(11):1257-1268. doi:10.7150/ijbs.12611
NF-κB-DICER-miRs Axis Regulates TNF-α Expression in Responses to Endotoxin Stress
1. Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, 110122, China
Unbalanced tumor necrosis factor (TNF)-α production is associated with pathogenesis of a variety of human diseases. However, the molecular pathways maintaining TNF-α homeostasis remain elusive. Here, we report that NF-κB/p65-DICER-miRs axis negatively regulates TNF-α production. We demonstrated that NF-κB bound to DICER promoter and transcriptionally regulated DICER expression. In addition, the NF-κB/DICER signaling suppresses TNF-α expression by generating mature forms of miR-125b and miR-130a which negatively regulate TNF-α mRNA. Furthermore, we showed that the hepatocyte-specific depletion of Dicer in mice resulted in TNF-α overproduction and sensitized the mice to endotoxin, which could be corrected by administration of miR-125b mimics. These data suggest that NF-κB/p65-DICER-miRs axis involved in maintaining of TNF-α homeostasis, and injection of miR-125b as a potential therapeutic method for septic shock.
Keywords: TNF-α/DICER/NF-κB/microRNAs/septic shock
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How to cite this article:
Guan Y, Yao H, Wang J, Sun K, Cao L, Wang Y. NF-κB-DICER-miRs Axis Regulates TNF-α Expression in Responses to Endotoxin Stress. Int J Biol Sci 2015; 11(11):1257-1268. doi:10.7150/ijbs.12611. Available from http://www.ijbs.com/v11p1257.htm