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Int J Biol Sci. 2015 Sep 9;11(11):1257-68. doi: 10.7150/ijbs.12611. eCollection 2015.

NF-κB-DICER-miRs Axis Regulates TNF-α Expression in Responses to Endotoxin Stress.

Author information

1
1. Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, 110122, China.
2
2. Laboratory of Neural Signal Transduction, Institute of Neuroscience, State Key Laboratory of Neuroscience, SIBS, Chinese Academy of Sciences, Shanghai, 200031, China.
3
3. Department of Medical Genetics, China Medical University, Shenyang, 110122, China.

Abstract

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

PMID:
26435691
PMCID:
PMC4582149
DOI:
10.7150/ijbs.12611
[Indexed for MEDLINE]
Free PMC Article

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