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论文题目: NF-kappa B-DICER-miRs Axis Regulates TNF-alpha Expression in Responses to Endotoxin Stress
英文论文题目: NF-kappa B-DICER-miRs Axis Regulates TNF-alpha Expression in Responses to Endotoxin Stress
第一作者: Guan, Y; Yao, HL; Wang, JF; Sun, KL; Cao, L; Wang, YZ
英文第一作者: Guan, Y; Yao, HL; Wang, JF; Sun, KL; Cao, L; Wang, YZ
联系作者: Cao, L (reprint author), China Med Univ, Key Lab Med Cell Biol, 77 Pu He Rd, Shenyang 110122, Peoples R China.
英文联系作者: Cao, L (reprint author), China Med Univ, Key Lab Med Cell Biol, 77 Pu He Rd, Shenyang 110122, Peoples R China.
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发表年度: 2015
卷: 11
期: 11
页码: 1257-1268
摘要: Unbalanced tumor necrosis factor (TNF)-alpha production is associated with pathogenesis of a variety of human diseases. However, the molecular pathways maintaining TNF-alpha homeostasis remain elusive. Here, we report that NF-kappa B/p65-DICER-miRs axis negatively regulates TNF-alpha production. We demonstrated that NF-kappa B bound to DICER promoter and transcriptionally regulated DICER expression. In addition, the NF-kappa B/DICER signaling suppresses TNF-alpha expression by generating mature forms of miR-125b and miR-130a which negatively regulate TNF-alpha mRNA. Furthermore, we showed that the hepatocyte-specific depletion of Dicer in mice resulted in TNF-alpha overproduction and sensitized the mice to endotoxin, which could be corrected by administration of miR-125b mimics. These data suggest that NF-kappa B/p65-DICER-miRs axis involved in maintaining of TNF-alpha homeostasis, and injection of miR-125b as a potential therapeutic method for septic shock.
英文摘要: Unbalanced tumor necrosis factor (TNF)-alpha production is associated with pathogenesis of a variety of human diseases. However, the molecular pathways maintaining TNF-alpha homeostasis remain elusive. Here, we report that NF-kappa B/p65-DICER-miRs axis negatively regulates TNF-alpha production. We demonstrated that NF-kappa B bound to DICER promoter and transcriptionally regulated DICER expression. In addition, the NF-kappa B/DICER signaling suppresses TNF-alpha expression by generating mature forms of miR-125b and miR-130a which negatively regulate TNF-alpha mRNA. Furthermore, we showed that the hepatocyte-specific depletion of Dicer in mice resulted in TNF-alpha overproduction and sensitized the mice to endotoxin, which could be corrected by administration of miR-125b mimics. These data suggest that NF-kappa B/p65-DICER-miRs axis involved in maintaining of TNF-alpha homeostasis, and injection of miR-125b as a potential therapeutic method for septic shock.
刊物名称: INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
英文刊物名称: INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
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学科: Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics
英文学科: Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics
影响因子: 4.509
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论文类别: Article
英文论文类别: Article
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