title: NF-κB-DICER-miRs Axis Regulates TNF-α Expression in Responses to Endotoxin Stress.
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.
authors.affiliation: 1. Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, 110122, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guan
authors.affiliation: 2. Laboratory of Neural Signal Transduction, Institute of Neuroscience, State Key Laboratory of Neuroscience, SIBS, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Hailan
authors.initials: H
authors.lastname: Yao
authors.affiliation: 2. Laboratory of Neural Signal Transduction, Institute of Neuroscience, State Key Laboratory of Neuroscience, SIBS, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: 3. Department of Medical Genetics, China Medical University, Shenyang, 110122, China.
authors.forename: Kailai
authors.initials: K
authors.lastname: Sun
authors.affiliation: 1. Key Laboratory of Medical Cell Biology, China Medical University, Shenyang, 110122, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Cao
authors.affiliation: 2. Laboratory of Neural Signal Transduction, Institute of Neuroscience, State Key Laboratory of Neuroscience, SIBS, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Yizheng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004731:Endotoxins / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043244:Ribonuclease III / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D004731:Endotoxins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
keywords: TNF-α/DICER/NF-κB/microRNAs/septic shock