MicroRNAs and signaling networks involved in epithelial–mesenchymal transition

Shenas, Mohammad Hossein Musavi; Eghbal‐Fard, Shadi; Mehrisofiani, Vahid; Yazdani, Nima Abd; Farzam, Omid Rahbar; Marofi, Faroogh

doi:10.1002/jcp.27489

Cited by 30 publications

(19 citation statements)

References 94 publications

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“…Other research has shown that miR-206 inhibits autocrine production of TGF-β as well as downstream neuropilin-1 (NRP1) and SMAD2 expression, resulting in decreased migration, invasion, and EMT in breast cancer cells [117]. Several other miRNAs, such as miR-373, miR-655, miR206, miR-155, miR-140-5p, miR-494, miR-125a/b, and miR-375, have been implicated in EMT [118,119,120,121,122]. However, for many of these factors, their specific functions remain to be elucidated.…”

Section: Tgf-β-induced Tumor Promoting Effectsmentioning

confidence: 99%

TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis

Yang

Baker

Dijke

2019

IJMS

718

597

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Transforming growth factor β (TGF-β) is a secreted cytokine that regulates cell proliferation, migration, and the differentiation of a plethora of different cell types. Consistent with these findings, TGF-β plays a key role in controlling embryogenic development, inflammation, and tissue repair, as well as in maintaining adult tissue homeostasis. TGF-β elicits a broad range of context-dependent cellular responses, and consequently, alterations in TGF-β signaling have been implicated in many diseases, including cancer. During the early stages of tumorigenesis, TGF-β acts as a tumor suppressor by inducing cytostasis and the apoptosis of normal and premalignant cells. However, at later stages, when cancer cells have acquired oncogenic mutations and/or have lost tumor suppressor gene function, cells are resistant to TGF-β-induced growth arrest, and TGF-β functions as a tumor promotor by stimulating tumor cells to undergo the so-called epithelial-mesenchymal transition (EMT). The latter leads to metastasis and chemotherapy resistance. TGF-β further supports cancer growth and progression by activating tumor angiogenesis and cancer-associated fibroblasts and enabling the tumor to evade inhibitory immune responses. In this review, we will consider the role of TGF-β signaling in cell cycle arrest, apoptosis, EMT and cancer cell metastasis. In particular, we will highlight recent insights into the multistep and dynamically controlled process of TGF-β-induced EMT and the functions of miRNAs and long noncoding RNAs in this process. Finally, we will discuss how these new mechanistic insights might be exploited to develop novel therapeutic interventions.

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Section: Tgf-β-induced Tumor Promoting Effectsmentioning

confidence: 99%

TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis

Yang

Baker

Dijke

2019

IJMS

718

597

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“…There are two major methods for gene therapy: The first one is direct gene transfer by using viral and nonviral vectors and the second one is gene delivery using genetically modified cells (ex vivo gene therapy; Seow & Wood, ). Viral vectors have high efficiency as the delivery vehicle of functional genes and has gone under clinical trials (Seow & Wood, ), but they have disadvantages, these include: Llimited effect, host immune response against these vectors, safety problems (Bessis, GarciaCozar, & Boissier, ), and low transduction efficiency restricting the use of this vectors (Musavi Shenas et al, ; Nayak & Herzog, ). While the recruitment of cells as a transfer platform of therapeutic useful proteins and genes has several advantages including (a) After ex vivo transduction of cells, the remains of the viral components are removed and the risk of unintentionally spreading of virus reduced (Harrington et al, ).…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells as carrier of the therapeutic agent in the gene therapy of blood disorders

Shomali

Gharibi

Vahedi

et al. 2019

Journal Cellular Physiology

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Nonhematopoietic stem cells as a delivery platform of therapeutic useful genes have attracted widespread attention in recent years, owing to gained a long lifespan, easy separation, high proliferation, and high transfection capacity. Mesenchymal stem/ stromal cells (MSCs) are the choice of the cells for gene and cell therapy due to high self-renewal capacity, high migration rate to the site of the tumor, and with immune suppressive and anti-inflammatory properties. Hence, it has a high potential of safety genetic modification of MSCs for antitumor gene expression and has paved the way for the clinical application of these cells to target the therapy of cancers and other diseases. The aim of gene therapy is targeted treatment of cancers and diseases through recovery, change, or enhancement cell performance to the sustained secretion of useful therapeutic proteins and induction expression of the functional gene in intended tissue. Recent developments in the vectors designing leading to the increase and durability of expression and improvement of the safety of the vectors that overcome a lot of problems, such as durability of expression and the host immune response. Nowadays, gene therapy approach is used by MSCs as a delivery vehicle in the preclinical and the clinical trials for the secretion of erythropoietin, recombinant antibodies, coagulation factors, cytokines, as well as angiogenic inhibitors in many blood disorders like anemia, hemophilia, and malignancies. In this study, we critically discuss the status of gene therapy by MSCs as a delivery vehicle for the treatment of blood disorders. Finally, the results of clinical trial studies are assessed, highlighting promising advantages of this emerging technology in the clinical setting.

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“…Small noncoding microRNAs (miRNAs) that are differentially expressed in normal tissues and cancers contribute to cancer development and progression [6,7]. miRNAs can function as oncomiRs through enforcing cancer metastasis in ccRCC [8,9]. Therefore, strategies that target oncomiRs may be alternative manners to overcome ccRCC metastasis.…”

mentioning

confidence: 99%

HMGA1-mediated miR-671-5p targets APC to promote metastasis of clear cell renal cell carcinoma through Wnt signaling

Chi¹,

Meng²,

Ding³

et al. 2020

neo

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This study aimed to investigate the effect of miR-671-5p on metastasis of clear cell renal cell carcinoma (ccRCC) and underlying mechanism involved. The migration and invasion of ccRCC cells were determined by transwell and boyden assays in vitro and in vivo. Genes mRNA and protein expression were detected by quantitative polymerase chain reaction (qPCR) and western blot analysis, respectively. The target gene of miRNA was confirmed by luciferase reporter assays. Transcriptional regulation of miRNA by transcription factor was detected by chromatin immunoprecipitation assay (ChIP). The expressions of miRNA in clinical specimens were detected by in situ hybridization (ISH). miR-671-5p promoted migration and invasion of ccRCC in vivo and in vitro. Moreover, miR-671-5p directly targeted APC to activate Wnt signaling, thus inducing the epithelial-mesenchymal transition (EMT) in ccRCC. Intriguingly, miR-671-5p expression was transcriptionally enhanced by HMGA1. Consistently, bioinformatics analysis suggested that HMGA1 was positively correlated with miR-671 expression; however, miR-671 was negatively correlated with APC. In situ hybridization analysis showed that miR-671-5p was upregulated in ccRCC compared with paracarcinoma and correlated with poor prognosis of ccRCC patients. In addition, univariate and multivariate analysis indicated that miR-671-5p expression was an independent prognostic factor for overall survival in ccRCC patients. Our data suggest that miR-671-5p is a tumor enhancer in regulating of ccRCC metastasis, and miR-671-5p may be utilized as a factor for the clinical diagnosis and prognosis of ccRCC.

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MicroRNAs and signaling networks involved in epithelial–mesenchymal transition

Cited by 30 publications

References 94 publications

TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis

TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis

Mesenchymal stem cells as carrier of the therapeutic agent in the gene therapy of blood disorders

HMGA1-mediated miR-671-5p targets APC to promote metastasis of clear cell renal cell carcinoma through Wnt signaling

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