title: A negative feedback loop between miR-200b and the nuclear factor-κB pathway via IKBKB/IKK-β in breast cancer cells.
abstract: MicroRNAs (miRNAs) 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.
authors.affiliation: Department of Critical Care Medicine, The Affiliated Tumour Hospital of Zhengzhou University, Jinshui, Henan, China.
authors.forename: Hewen
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Translational Imaging, Houston Methodist Hospital, TX, USA.|Department of Internal Medicine, The Affiliated Tumour Hospital of Zhengzhou University, Jinshui, Henan, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Critical Care Medicine, The Affiliated Tumour Hospital of Zhengzhou University, Jinshui, Henan, China.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Critical Care Medicine, The Affiliated Tumour Hospital of Zhengzhou University, Jinshui, Henan, China.
authors.forename: Shan
authors.initials: S
authors.lastname: An
authors.affiliation: Department of Critical Care Medicine, The Affiliated Tumour Hospital of Zhengzhou University, Jinshui, Henan, China.
authors.forename: Peijun
authors.initials: P
authors.lastname: Ye
authors.affiliation: Department of Internal Medicine, The Affiliated Tumour Hospital of Zhengzhou University, Jinshui, Henan, China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Luo
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051550:I-kappa B Kinase / Q000096:biosynthesis / Q000235:genetics*; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000235:genetics*
chemical_list: C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C498143:RELA protein, human; D051996:Transcription Factor RelA; D051550:I-kappa B Kinase; C496560:IKBKB protein, human
keywords: IKBKB; breast cancer cells; miR-200b; microRNA; nuclear factor-κB (NF-κB)