Premium
A negative feedback loop between miR‐200b and the nuclear factor‐κB pathway via IKBKB / IKK ‐β in breast cancer cells
Author(s) -
Wu Hewen,
Wang Guohui,
Wang Zhengwei,
An Shan,
Ye Peijun,
Luo Suxia
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13543
Subject(s) - gene knockdown , downregulation and upregulation , iκbα , nf κb , cancer research , signal transduction , biology , microbiology and biotechnology , gene , biochemistry
Micro RNA s (mi RNA s) act as important post‐transcriptional regulators of gene expression in diverse signalling pathways. However, the relationship between miR‐200b and the nuclear factor‐κB ( NF ‐κB) signalling pathway remains poorly understood in breast cancer cells. In the current study, we show that IKBKB is a direct target of miR‐200b, and that miR‐200b downregulates IKBKB expression via directly binding to its 3′‐ UTR . miR‐200b inhibits IκBα phosphorylation, nuclear p50/p65 expression, NF ‐κB‐binding activity, and the translocation of p65 to the nucleus. In addition, miR‐200b also suppresses tumour necrosis factor ( TNF )‐α‐induced NF ‐κB activation and the expression of NF ‐κB target genes. Importantly, IKBKB overexpression attenuates the inhibitory roles of miR‐200b in NF ‐κB expression, NF ‐κB‐binding activity, and the nuclear translocation of p65. We also show that NF ‐κB p65 knockdown reduces the binding of NF ‐κB to the miR‐200b promoter and miR‐200b promoter activity. Furthermore, p65 knockdown or inhibition of IκBα phosphorylation suppresses miR‐200b expression. Finally, functional studies show that IKBKB overexpression can restore the cell growth and migration that are suppressed by miR‐200b. In conclusion, our results demonstrate that miR‐200b, a transcriptional target of NF ‐κB, suppresses breast cancer cell growth and migration, and NF ‐κB activation, through downregulation of IKBKB , indicating that miR‐200b has potential as a therapeutic target in breast cancer patients.