The epithelial-mesenchymal transition of glioma cells promotes tissue factor expression via the miR200a/ZEB1 axis

Sun, Ying; Jiang, Yining; Wang, Ying; Yu, Pengyue; Su, Xing; Song, Yanke; Wang, Min; Yao, Li; Zhao, Lei

doi:10.1016/j.brainres.2022.147782

Cited by 5 publications

(3 citation statements)

References 34 publications

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“…In a murine model, TF or ZEB1 silencing impaired the metastatic niches in the lungs [ 18 ]. Accordingly, Sun and co-workers showed the regulation of TF expression by the miR200a/ZEB1 axis in glioma cells [ 54 ]. In addition, Villard and collaborators showed that CD44, a CSC marker, controls the TF expression in the MDA-MB-468 breast cancer cell line, and, consequently, its procoagulant activity [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

TF/PAR2 Signaling Axis Supports the Protumor Effect of Neutrophil Extracellular Traps (NETs) on Human Breast Cancer Cells

Martins-Cardoso,

Maçao,

Souza

et al. 2023

Cancers

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Neutrophil extracellular traps (NETs) have been implicated in several hallmarks of cancer. Among the protumor effects, NETs promote epithelial-mesenchymal transition (EMT) in different cancer models. EMT has been linked to an enhanced expression of the clotting-initiating protein, tissue factor (TF), thus favoring the metastatic potential. TF may also exert protumor effects by facilitating the activation of protease-activated receptor 2 (PAR2). Herein, we evaluated whether NETs could induce TF expression in breast cancer cells and further promote procoagulant and intracellular signaling effects via the TF/PAR2 axis. T-47D and MCF7 cell lines were treated with isolated NETs, and samples were obtained for real-time PCR, flow cytometry, Western blotting, and plasma coagulation assays. In silico analyses were performed employing RNA-seq data from breast cancer patients deposited in The Cancer Genome Atlas (TCGA) database. A positive correlation was observed between neutrophil/NETs gene signatures and TF gene expression. Neutrophils/NETs gene signatures and PAR2 gene expression also showed a significant positive correlation in the bioinformatics model. In vitro analysis showed that treatment with NETs upregulated TF gene and protein expression in breast cancer cell lines. The inhibition of ERK/JNK reduced the TF gene expression induced by NETs. Remarkably, the pharmacological or genetic inhibition of the TF/PAR2 signaling axis attenuated the NETs-induced expression of several protumor genes. Also, treatment of NETs with a neutrophil elastase inhibitor reduced the expression of metastasis-related genes. Our results suggest that the TF/PAR2 signaling axis contributes to the pro-cancer effects of NETs in human breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

TF/PAR2 Signaling Axis Supports the Protumor Effect of Neutrophil Extracellular Traps (NETs) on Human Breast Cancer Cells

Martins-Cardoso,

Maçao,

Souza

et al. 2023

Cancers

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“…Many miRNAs are indicated as potential biomarkers in cancer, and the fact that they can be utilised in terms of their diagnostic and/or prognostic value is still extensively studied [39,[74][75][76][77]. Among the ZEB family-related miRNAs, there are also a few examples.…”

Section: Predicting Prognosismentioning

confidence: 99%

Zinc Finger E-Box Binding Homeobox Family: Non-Coding RNA and Epigenetic Regulation in Gliomas

Lenda,

Żebrowska-Nawrocka,

Turek

et al. 2023

Biomedicines

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Gliomas are the most common malignant brain tumours. Among them, glioblastoma (GBM) is a grade four tumour with a median survival of approximately 15 months and still limited treatment options. Although a classical epithelial to mesenchymal transition (EMT) is not the case in glioma due to its non-epithelial origin, the EMT-like processes may contribute largely to the aggressive and highly infiltrative nature of these tumours, thus promoting invasive phenotype and intracranial metastasis. To date, many well-known EMT transcription factors (EMT-TFs) have been described with clear, biological functions in glioma progression. Among them, EMT-related families of molecules such as SNAI, TWIST and ZEB are widely cited, well-established oncogenes considering both epithelial and non-epithelial tumours. In this review, we aimed to summarise the current knowledge with a regard to functional experiments considering the impact of miRNA and lncRNA as well as other epigenetic modifications, with a main focus on ZEB1 and ZEB2 in gliomas. Although we explored various molecular interactions and pathophysiological processes, such as cancer stem cell phenotype, hypoxia-induced EMT, tumour microenvironment and TMZ-resistant tumour cells, there is still a pressing need to elucidate the molecular mechanisms by which EMT-TFs are regulated in gliomas, which will enable researchers to uncover novel therapeutic targets as well as improve patients’ diagnosis and prognostication.

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“…miR-200a-3p, a typical microRNA that regulates EMT, often targets zinc finger E-box binding homeobox 1 (ZEB1) to play a regulatory role in various diseases. 15,16 ZEB1 belongs to the zinc finger E-box binding homeobox family of zinc finger/homeodomain transcriptional repressors, which have been reported to be critical factors in EMT. 17 ZEB1 plays a vital role in the downregulation of Ecadherin.…”

Section: Introductionmentioning

confidence: 99%

miR‐200a‐3p regulates epithelial–mesenchymal transition and inflammation in chronic rhinosinusitis with nasal polyps by targeting ZEB1 via ERK/p38 pathway

Sun

et al. 2023

Int Forum Allergy Rhinol

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BackgroundSeveral biological processes are regulated by miR‐200a‐3p, including cell proliferation, migration, and epithelial–mesenchymal transition (EMT). In this study we aimed to uncover the diagnostic value and molecular mechanisms of miR‐200a‐3p in chronic rhinosinusitis with nasal polyps (CRSwNP).MethodsThe expressions of miR‐200a‐3p were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR), Zinc finger E‐box binding homeobox 1 (ZEB1) levels were examined by qRT‐PCR and immunofluorescence staining. The interaction between miR‐200a‐3p and ZEB1 was predicted by TargetScan Human 8.0 and confirmed by dual‐luciferase reporter assays. In addition, the effect of miR‐200a‐3p and ZEB1 on EMT‐related makers and inflammation cytokines was assessed by qRT‐PCR and Western blotting in human nasal epithelial cells (hNEpCs) and primary human nasal mucosal epithelial cells (hNECs).ResultsWe found that miR‐200a‐3p was downregulated in non‐eosinophilic and eosinophilic CRSwNP patients when compared with controls. The diagnostic value of miR‐200a‐3p in serum is reflected by the receiver operating characteristic curve and the 22‐item Sino‐Nasal Outcome Test. Bioinformatic analysis and luciferase reporter assay identified ZEB1 as a target of miR‐200a‐3p. ZEB1 was more highly expressed in CRSwNP than in controls. Furthermore, miR‐200a‐3p inhibitor or ZEB1 overexpression significantly suppressed the epithelial marker E‐cadherin; promoted the activation of vimentin, α‐spinal muscle atrophy, and N‐cadherin; and aggravated inflammation in hNEpCs. Knockdown of ZEB1 significantly alleviated the cellular remodeling caused by miR‐200a‐3p inhibitor via the extracellular signal‐regulated kinase (ERK)/p38 pathway in hNECs.ConclusionsmiR‐200a‐3p suppresses EMT and inflammation by regulating the expression of ZEB1 via the ERK/p38 pathway. Our study presents new ideas for protecting nasal epithelial cells from tissue remodeling and finding a possible target for disease.

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The epithelial-mesenchymal transition of glioma cells promotes tissue factor expression via the miR200a/ZEB1 axis

Cited by 5 publications

References 34 publications

TF/PAR2 Signaling Axis Supports the Protumor Effect of Neutrophil Extracellular Traps (NETs) on Human Breast Cancer Cells

TF/PAR2 Signaling Axis Supports the Protumor Effect of Neutrophil Extracellular Traps (NETs) on Human Breast Cancer Cells

Zinc Finger E-Box Binding Homeobox Family: Non-Coding RNA and Epigenetic Regulation in Gliomas

miR‐200a‐3p regulates epithelial–mesenchymal transition and inflammation in chronic rhinosinusitis with nasal polyps by targeting ZEB1 via ERK/p38 pathway

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