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

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...

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Autores principales: Guan, Yi, Yao, Hailan, Wang, Junfeng, Sun, Kailai, Cao, Liu, Wang, Yizheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582149/
https://www.ncbi.nlm.nih.gov/pubmed/26435691
http://dx.doi.org/10.7150/ijbs.12611
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author Guan, Yi
Yao, Hailan
Wang, Junfeng
Sun, Kailai
Cao, Liu
Wang, Yizheng
author_facet Guan, Yi
Yao, Hailan
Wang, Junfeng
Sun, Kailai
Cao, Liu
Wang, Yizheng
author_sort Guan, Yi
collection PubMed
description 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.
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spelling pubmed-45821492015-10-02 NF-κB-DICER-miRs Axis Regulates TNF-α Expression in Responses to Endotoxin Stress Guan, Yi Yao, Hailan Wang, Junfeng Sun, Kailai Cao, Liu Wang, Yizheng Int J Biol Sci Research Paper 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. Ivyspring International Publisher 2015-09-09 /pmc/articles/PMC4582149/ /pubmed/26435691 http://dx.doi.org/10.7150/ijbs.12611 Text en © 2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
spellingShingle Research Paper
Guan, Yi
Yao, Hailan
Wang, Junfeng
Sun, Kailai
Cao, Liu
Wang, Yizheng
NF-κB-DICER-miRs Axis Regulates TNF-α Expression in Responses to Endotoxin Stress
title NF-κB-DICER-miRs Axis Regulates TNF-α Expression in Responses to Endotoxin Stress
title_full NF-κB-DICER-miRs Axis Regulates TNF-α Expression in Responses to Endotoxin Stress
title_fullStr NF-κB-DICER-miRs Axis Regulates TNF-α Expression in Responses to Endotoxin Stress
title_full_unstemmed NF-κB-DICER-miRs Axis Regulates TNF-α Expression in Responses to Endotoxin Stress
title_short NF-κB-DICER-miRs Axis Regulates TNF-α Expression in Responses to Endotoxin Stress
title_sort nf-κb-dicer-mirs axis regulates tnf-α expression in responses to endotoxin stress
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582149/
https://www.ncbi.nlm.nih.gov/pubmed/26435691
http://dx.doi.org/10.7150/ijbs.12611
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