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miRNA-129/FBW7/NF-κB, a Novel Regulatory Pathway in Inflammatory Bowel Disease.

Abstract：

:F-box and WD repeat domain-containing protein 7 (FBW7) has been documented to be implicated in nuclear factor κB (NF-κB) signaling and inflammation, but its role in the pathogenesis of inflammatory bowel disease (IBD) remains unknown. FBW7 was increased both in colon tissues from IBD patients and trinitrobenzene sulphonic acid (TNBS)-induced colitis mice. Immunoprecipitation assay identified that FBW7 as a novel inhibitor of κBα (IκBα)-binding partner. FBW7 upregulation promoted IκBα ubiquitin-dependent degradation, NF-κB activation, and subsequent intestinal inflammation in intestinal epithelial cells, whereas inhibition of FBW7 produced the opposite effects. Computational analysis revealed that microRNA-129 (miR-129) directly targets at 3' UTR of FBW7. The miR-129-suppressed proteasome pathway mediated the degradation of IκBα by negatively regulating FBW7. The in vivo study demonstrated that upregulation of miR-129 ameliorated intestinal inflammation in TNBS-induced colitis mice through inhibition of the NF-κB signaling pathway. In conclusion, FBW7 is a novel E3 ubiquitin ligase for IκBα and thereby leads to NF-κB activation and inflammation. miR-129 negatively regulates FBW7 expression, resulting in secondary inhibition of the NF-κB pathway and amelioration of intestinal inflammation. Our findings provide new insight into the development of therapeutic strategies for the treatment of IBD.

journal_name

Mol Ther Nucleic Acids

journal_title

Molecular therapy. Nucleic acids

authors

Meng Q,Wu W,Pei T,Xue J,Xiao P,Sun L,Li L,Liang D

doi

10.1016/j.omtn.2019.10.048

subject

Has Abstract

pub_date

2020-03-06 00:00:00

pages

731-740

issn

2162-2531

pii

S2162-2531(19)30386-5

journal_volume

19

pub_type

杂志文章

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