DNA Damage Induces NF-κB-dependent MicroRNA-21 Up-regulation and Promotes Breast Cancer Cell Invasion

Niu, Jia; Shi, Yujun; Tan, Guangyun; Yang, Chuan; Fan, Meiyun; Pfeffer, Lawrence M.; Wu, Zhao-Hui

doi:10.1074/jbc.m112.355495

Cited by 146 publications

(131 citation statements)

References 59 publications

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“…STAT3, a crucial gene in progression of HNSCC, has been previously suggested to up‐regulate miR‐21, in a NF‐κB‐dependent form of IL‐6 up‐regulation 34. Our data from immunofluorescence assay demonstrated that the acidic bile‐induced activated STAT3 and NF‐κB were inhibited by NF‐κB inhibitor in treated HHPC (Figure 6).…”

Section: Resultssupporting

confidence: 59%

NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

Doukas¹,

Vageli²,

Sasaki³

2018

J Cellular Molecular Medi

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We previously demonstrated that acidic bile activates NF‐κB, deregulating the expression of oncogenic miRNA markers, in pre‐malignant murine laryngopharyngeal mucosa. Here, we hypothesize that the in vitro exposure of human hypopharyngeal cells to acidic bile deregulates cancer‐related miRNA markers that can be reversed by BAY 11‐7082, a pharmacologic NF‐κB inhibitor. We repetitively exposed normal human hypopharyngeal primary cells and human hypopharyngeal keratinocytes to bile fluid (400 μmol/L), at pH 4.0 and 7.0, with/without BAY 11‐7082 (20 μmol/L). We centred our study on the transcriptional activation of oncogenic miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375, miR‐451a and NF‐κB‐related genes, previously linked to acidic bile‐induced pre‐neoplastic events. Our novel findings in vitro are consistent with our hypothesis demonstrating that BAY 11‐7082 significantly reverses the acidic bile‐induced oncogenic miRNA phenotype, in normal hypopharyngeal cells. BAY 11‐7082 strongly inhibits the acidic bile‐induced up‐regulation of miR‐192 and down‐regulation of miR‐451a and significantly decreases the miR‐21/375 ratios, previously related to poor prognosis in hypopharyngeal cancer. This is the first in vitro report that NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in normal human hypopharyngeal cells, suggesting that acidic bile‐induced events are directly or indirectly dependent on NF‐κB signalling.

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Section: Resultssupporting

confidence: 59%

NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

Doukas¹,

Vageli²,

Sasaki³

2018

J Cellular Molecular Medi

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“…Additionally, anti-apoptosis approaches signi cantly improved CVB3-induced heart injury [32,33], further con rming the pathological role of apoptosis in the acute myocarditis. Our results were in line with previous studies that show miR-21 targeting PDCD4 to produce antiapoptotic e ect; however, these studies are mainly focused on the elds of tumor [34][35][36] and vascular diseases [37,38]. Only a few studies report that miR-21 exerts an anti-apoptotic e ect by targeting PDCD4 in heart diseases.…”

Section: Discussionsupporting

confidence: 92%

MiR-21 confers resistance against CVB3-induced myocarditis by inhibiting PDCD4-mediated apoptosis

He¹,

Yan²,

Dong³

et al. 2013

CIM

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MiR-21 confers resistance against CVB3-induced myocarditis by inhibiting PDCD4-mediated apoptosis AbstractPurpose: e participation of microRNAs (miRNAs) in cardiovascular diseases suggests them as potential targets for novel preventive and therapeutic strategies. In this study, the key myocardial miRNA, miR-21, was identi ed in the murine coxsackievirus B3 (CVB3)-induced myocarditis model and its contribution to disease progression was explored.Methods: Myocardial microRNA expression changes in CVB3-infected mice were analyzed by real-time PCR and miR-21 was found to be the miRNA whose expression was signi cantly reduced. Mice were injected with plasmid encoding miR-21 (pMDH-miR-21) at day 1 post CVB3 infection and myocarditis severity was evaluated 7 days postinfection. e underlying mechanism of miR-21 in viral myocarditis was also investigated.Results: Myocardial miR-21 expression was negatively related to viral myocarditis severity. Recovery of miR-21 expression, by injecting with pMDH-miR-21, signi cantly relieved CVB3-induced myocarditis as shown by increased body weight, reduced myocardial injury, lowered myocarditis score and increased survival rate. Further study showed that miR-21 could protect myocardial apoptosis by speci cally inhibiting its target programmed cell death 4 (PDCD4) expression.Conclusion: miR-21 administration e ciently alleviated CVB3-induced myocarditis by repressing PDCD4-mediated apoptosis. Our study not only helps to better understand the pathogenesis of viral myocarditis, but also proves the potential of miR-21 as a novel therapeutic target for treatment of CVB3-induced myocarditis and other apoptosis-mediated cardiovascular diseases.

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“…8B). Our previous studies have demonstrated that the transcription of these genes in response to genotoxic stress is regulated by NF-B, which may contribute to reduced apoptosis and prolonged cell survival upon DNA damage (5,16,18). Accordingly, we found that genotoxic drug-induced apoptosis was attenuated in TANK KO cells compared with wild-type cells (Fig.…”

Section: The Tank-mcpip1-usp10 Complex Inhibits Il-1r/tlrmediated Nf-mentioning

confidence: 58%

TRAF Family Member-associated NF-κB Activator (TANK) Inhibits Genotoxic Nuclear Factor κB Activation by Facilitating Deubiquitinase USP10-dependent Deubiquitination of TRAF6 Ligase

Wang

Huang

Xiao

et al. 2015

Journal of Biological Chemistry

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Background: TANK has been shown to promote deubiquitination of TRAFs, but the mechanism involved is unclear. Results: TANK associates with MCPIP1 and USP10, thereby diminishing TRAF6 ubiquitination, which inhibits NF-B activation by genotoxic stress and IL-1R/TLR activation. Conclusion:The deubiquitinating activity of TANK is achieved by its association with USP10. Significance: Modulating TANK may enhance cancer cell sensitivity to chemotherapy.

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DNA Damage Induces NF-κB-dependent MicroRNA-21 Up-regulation and Promotes Breast Cancer Cell Invasion

Cited by 146 publications

References 59 publications

NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

NF‐κB inhibition reverses acidic bile‐induced miR‐21, miR‐155, miR‐192, miR‐34a, miR‐375 and miR‐451a deregulations in human hypopharyngeal cells

MiR-21 confers resistance against CVB3-induced myocarditis by inhibiting PDCD4-mediated apoptosis

TRAF Family Member-associated NF-κB Activator (TANK) Inhibits Genotoxic Nuclear Factor κB Activation by Facilitating Deubiquitinase USP10-dependent Deubiquitination of TRAF6 Ligase

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