Int J Biol Sci 2015; 11(11):1257-1268. doi:10.7150/ijbs.12611 This issue
1. Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, 110122, China
2. Laboratory of Neural Signal Transduction, Institute of Neuroscience, State Key Laboratory of Neuroscience, SIBS, Chinese Academy of Sciences, Shanghai, 200031, China
3. Department of Medical Genetics, China Medical University, Shenyang, 110122, China
#These authors contributed equally to this work.
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