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NF-?B-DICER-miRs Axis Regulates TNF-? Expression in Responses to Endotoxin Stress.

ABSTRACT: Unbalanced tumor necrosis factor (TNF)-? production is associated with pathogenesis of a variety of human diseases. However, the molecular pathways maintaining TNF-? homeostasis remain elusive. Here, we report that NF-?B/p65-DICER-miRs axis negatively regulates TNF-? production. We demonstrated that NF-?B bound to DICER promoter and transcriptionally regulated DICER expression. In addition, the NF-?B/DICER signaling suppresses TNF-? expression by generating mature forms of miR-125b and miR-130a which negatively regulate TNF-? mRNA. Furthermore, we showed that the hepatocyte-specific depletion of Dicer in mice resulted in TNF-? overproduction and sensitized the mice to endotoxin, which could be corrected by administration of miR-125b mimics. These data suggest that NF-?B/p65-DICER-miRs axis involved in maintaining of TNF-? homeostasis, and injection of miR-125b as a potential therapeutic method for septic shock.

SUBMITTER: Guan Y 

PROVIDER: S-EPMC4582149 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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

Guan Yi Y   Yao Hailan H   Wang Junfeng J   Sun Kailai K   Cao Liu L   Wang Yizheng Y  

International journal of biological sciences 20150909 11

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  ...[more]

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