NF-kB-regulated exosomal miR-155 promotes the inflammation associated with arsenite carcinogenesis

Chen, Chao; Luo, Fei; Liu, Xinlu; Lu, Lu; Xu, Hui; Yang, Qianlei; Xue, Junchao; Shi, Le; Li, Jun; Zhang, Aihua; Liu, Qizhan

doi:10.1016/j.canlet.2016.11.027

Cited by 97 publications

(58 citation statements)

References 62 publications

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“…Similar findings were reported by Wei et al, wherein exosomal release of miR-221/222 conveyed tamoxifen resistance to breast cancer cells [62]. Other studies have shown that exosomal miRNA-155 is inflammogenic through IL6 and IL8 upregulation [64], while exosomal miRNA-214-3p can inhibit bone development by interfering with osteogenic transcription factors [36], highlighting the wide range of deleterious health effects that exosomal/EV miRNAs are capable of mediating. Angiogenesis is associated with both negative health outcomes (e.g., tumor growth) and beneficial outcomes (e.g., wound healing and the resolution of cardiovascular disease), and EVs are capable of increasing angiogenesis [65][66][67].…”

Section: Disease and Exosomal Mirnassupporting

confidence: 80%

The Therapeutic Potential of Breast Milk-Derived Extracellular Vesicles

Galley

Besner

2020

Nutrients

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In the past few decades, interest in the therapeutic benefits of exosomes and extracellular vesicles (EVs) has grown exponentially. Exosomes/EVs are small particles which are produced and exocytosed by cells throughout the body. They are loaded with active regulatory and stimulatory molecules from the parent cell including miRNAs and enzymes, making them prime targets in therapeutics and diagnostics. Breast milk, known for years to have beneficial health effects, contains a population of EVs which may mediate its therapeutic effects. This review offers an update on the therapeutic potential of exosomes/EVs in disease, with a focus on EVs present in human breast milk and their remedial effect in the gastrointestinal disease necrotizing enterocolitis. Additionally, the relationship between EV miRNAs, health, and disease will be examined, along with the potential for EVs and their miRNAs to be engineered for targeted treatments.

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Section: Disease and Exosomal Mirnassupporting

confidence: 80%

The Therapeutic Potential of Breast Milk-Derived Extracellular Vesicles

Galley

Besner

2020

Nutrients

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“…In summary, we have shown that horizontal transfer of cancer EV cargo following internalization results in malignant transformation of clinically indolent urothelial cells, and inhibition of EV internalization by small inhibiting compounds mitigates the transformative potential of cancer EVs (40). Critically, cells were evaluated following the withdrawal of cancer EVs and after a recovery period in normal culture for at least 5 weeks, indicating that the neoplastic changes were persistent.…”

Section: Suppression Of Er Stress Inhibits Ev-induced Transformationmentioning

confidence: 95%

Bladder cancer extracellular vesicles drive tumorigenesis by inducing the unfolded protein response in endoplasmic reticulum of nonmalignant cells

Wu¹,

Silvers

Messing

et al. 2019

Journal of Biological Chemistry

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The field cancerization effect has been proposed to explain bladder cancer's multifocal and recurrent nature, yet the mechanisms of this effect remain unknown. In this work, using cell biology, flow cytometry, and qPCR analyses, along with a xenograft mouse tumor model, we show that chronic exposure to tumor-derived extracellular vesicles (TEVs) results in the neoplastic transformation of nonmalignant human SV-HUC urothelial cells. Inhibition of EV uptake prevented this transformation. Transformed cells not only possessed several oncogenic properties, such as increased genome instability, loss of cellcell contact inhibition, and invasiveness, but also displayed altered morphology and cell structures, such as an enlarged cytoplasm with disrupted endoplasmic reticulum (ER) alignment and the accumulation of smaller mitochondria. Exposure of SV-HUC cells to TEVs provoked the unfolded protein response in the endoplasmic reticulum (UPR ER). Prolonged induction of UPR ER signaling activated the survival branch of the UPR ER pathway, in which cells had elevated expression of inositol-requiring enzyme 1 (IRE1), NF-B, and the inflammatory cytokine leptin, and incurred loss of the pro-apoptotic protein C/EBP homologous protein (CHOP). More importantly, inhibition of ER stress by docosahexaenoic acid prevented TEVinduced transformation. We propose that TEVs promote malignant transformation of predisposed cells by inhibiting pro-apoptotic signals and activating tumor-promoting ER stressinduced unfolded protein response and inflammation. This study provides detailed insight into the mechanisms underlying the bladder cancer field effect and tumor recurrence.

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“…Moreover, the expression of the inflammatory cytokines, including IL-6 and TNF-, can be down-regulated by inhibiting the activation of free-radicalactivated transcription factors, such as transcription factor nuclear factor-B (NF-B), which provides a critical link between inflammation and tumour (Karin, 2009). It has been observed that NF-B activation is a result of underlying inflammation or a consequence of the formation of an inflammatory microenvironment during tumour progression (Chen et al, 2017). These observations suggest that NF-B is a potential target for the design of new anticancer drugs with anti-inflammatory activity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, crystal structures and anti-inflammatory activity of four 3,5-bis(arylidene)-N-benzenesulfonyl-4-piperidone derivatives

Bai

Zhang

et al. 2018

Acta Crystallogr C

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of the olefinic double bonds. Molecules of both (4) and (6) are connected by hydrogen bonds into one-dimensional chains. In (5) and (7), pairs of adjacent molecules embrace through intermolecular hydrogen bonds to form a bimolecular combination, which are further extended into a two-dimensional sheet. The anti-inflammatory activity data reveal that (4)-(7) significantly inhibit LPS-induced interleukin (IL-6) and tumour necrosis factor (TNF-) secretion. Most importantly, (6) and (7), with strong electron-withdrawing substituents, display more potential inhibitory effects than (4) and (5).

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NF-kB-regulated exosomal miR-155 promotes the inflammation associated with arsenite carcinogenesis

Cited by 97 publications

References 62 publications

The Therapeutic Potential of Breast Milk-Derived Extracellular Vesicles

The Therapeutic Potential of Breast Milk-Derived Extracellular Vesicles

Bladder cancer extracellular vesicles drive tumorigenesis by inducing the unfolded protein response in endoplasmic reticulum of nonmalignant cells

Synthesis, crystal structures and anti-inflammatory activity of four 3,5-bis(arylidene)-N-benzenesulfonyl-4-piperidone derivatives

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