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International Journal Of Bilogical Sciences

.: Home > International Journal Of Bilogical Sciences > 2015 > Volume 11 Number 11 > Yi Guan1, Hailan Yao2, Junfeng Wang2, Kailai Sun3,Liu Cao1 .and Yizheng Wang2

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

Yi Guan1, Hailan Yao2, Junfeng Wang2, Kailai Sun3,Liu Cao1 .and Yizheng Wang2
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. Corresponding authors: Liu Cao, Key Laboratory of Medical Cell Biology, China Medical University, 77 Pu-He Road, Shenyang, 110122, P.R.China. Email: caoliu@mail.cmu.edu.cn or Yizheng Wang, Institute of Neuroscience, SIBS, 320 Yue-Yang Road, Shanghai, 200031, P. R. China. Email: yzwang@ion.ac.cn
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

Date Deposited : 08 Mar 2016 10:54

Last Modified : 08 Mar 2016 10:54

Official URL: http://www.ijbs.com/v11i11

Volume 11, Number 11, - 2015 , ISSN 1449-2288

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