scholarly journals Metastatic EMT Phenotype Is Governed by MicroRNA-200-Mediated Competing Endogenous RNA Networks

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 73
Author(s):  
Sara Uhan ◽  
Nina Hauptman
Keyword(s):  
Large Scale ◽  
Transcriptional Control ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Cell ◽  
Cell Phenotype ◽  
Competing Endogenous Rna ◽  
Protein Coding ◽  
Factors Affecting ◽  
Mesenchymal Transition ◽  
Metastatic Dissemination

Epithelial–mesenchymal transition (EMT) is a fundamental physiologically relevant process that occurs during morphogenesis and organ development. In a pathological setting, the transition from epithelial toward mesenchymal cell phenotype is hijacked by cancer cells, allowing uncontrolled metastatic dissemination. The competing endogenous RNA (ceRNA) hypothesis proposes a competitive environment resembling a large-scale regulatory network of gene expression circuits where alterations in the expression of both protein-coding and non-coding genes can make relevant contributions to EMT progression in cancer. The complex regulatory diversity is exerted through an array of diverse epigenetic factors, reaching beyond the transcriptional control that was previously thought to single-handedly govern metastatic dissemination. The present review aims to unravel the competitive relationships between naturally occurring ceRNA transcripts for the shared pool of the miRNA-200 family, which play a pivotal role in EMT related to cancer dissemination. Upon acquiring more knowledge and clinical evidence on non-genetic factors affecting neoplasia, modulation of the expression levels of diverse ceRNAs may allow for the development of novel prognostic/diagnostic markers and reveal potential targets for the disruption of cancer-related EMT.

scholarly journals Modulation of Epithelial to Mesenchymal Transition Signaling Pathways by Olea Europaea and Its Active Compounds

2019 ◽  
Vol 20 (14) ◽  
pp. 3492 ◽  
Author(s):  
Rabiatul Adawiyah Razali ◽  
Yogeswaran Lokanathan ◽  
Muhammad Dain Yazid ◽  
Ayu Suraya Ansari ◽  
Aminuddin Bin Saim ◽  
...  
Keyword(s):  
Olea Europaea ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Healing Process ◽  
Mesenchymal Cell ◽  
Cell Phenotype ◽  
Wound Healing Process ◽  
Active Compounds ◽  
Mesenchymal Transition ◽  
Olea Europaéa

Epithelial-mesenchymal transition (EMT) is a significant dynamic process that causes changes in the phenotype of epithelial cells, changing them from their original phenotype to the mesenchymal cell phenotype. This event can be observed during wound healing process, fibrosis and cancer. EMT-related diseases are usually caused by inflammation that eventually leads to tissue remodeling in the damaged tissue. Prolonged inflammation causes long-term EMT activation that can lead to tissue fibrosis or cancer. Due to activation of EMT by its signaling pathway, therapeutic approaches that modulate that pathway should be explored. Olea europaea (OE) is well-known for its anti-inflammatory effects and abundant beneficial active compounds. These properties are presumed to modulate EMT events. This article reviews recent evidence of the effects of OE and its active compounds on EMT events and EMT-related diseases. Following evidence from the literature, it was shown that OE could modulate TGFβ/SMAD, AKT, ERK, and Wnt/β-catenin pathways in EMT due to a potent active compound that is present therein.

scholarly journals Non-invasive detection of epithelial mesenchymal transition phenotype and metastatic dissemination of lung cancer by liquid biopsy

2021 ◽  
Author(s):  
Viviana De Rosa ◽  
Rosa Fonti ◽  
Silvana Del Vecchio ◽  
Francesca Iommelli
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Liquid Biopsy ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Cell ◽  
Mesenchymal Transition ◽  
Metastatic Dissemination ◽  
Lung Cancer Patients ◽  
Non Invasive

The occurrence of phenotype switch from an epithelial to a mesenchymal cell state during the activation of the epithelial mesenchymal transition (EMT) program in cancer cells has been closely associated with the generation of invasive tumor cells that contribute to metastatic dissemination and treatment failure. Liquid biopsy represents an emergent non-invasive tool that may improve our understanding of the molecular events leading to cancer progression and initiating the metastatic cascade through the dynamic analysis of tumor-derived components isolated from body fluids. The present review will primarily focus on the applications of liquid biopsy in lung cancer patients for identifying EMT signature, elucidating molecular mechanisms underlying the acquisition of an invasive phenotype and detecting new targets for therapy.

scholarly journals Functional antagonism of chromatin modulators regulates epithelial-mesenchymal transition

2021 ◽  
Vol 7 (9) ◽  
pp. eabd7974
Author(s):  
Michela Serresi ◽  
Sonia Kertalli ◽  
Lifei Li ◽  
Matthias Jürgen Schmitt ◽  
Yuliia Dramaretska ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Transcriptional Control ◽  
Molecular Mechanisms ◽  
Developmental Process ◽  
Epithelial Mesenchymal Transition ◽  
Chromatin Remodelers ◽  
Mesenchymal Transition ◽  
Signature Genes ◽  
Chromatin Regulators ◽  
The Impact

Epithelial-mesenchymal transition (EMT) is a developmental process hijacked by cancer cells to modulate proliferation, migration, and stress response. Whereas kinase signaling is believed to be an EMT driver, the molecular mechanisms underlying epithelial-mesenchymal interconversion are incompletely understood. Here, we show that the impact of chromatin regulators on EMT interconversion is broader than that of kinases. By combining pharmacological modulation of EMT, synthetic genetic tracing, and CRISPR interference screens, we uncovered a minority of kinases and several chromatin remodelers, writers, and readers governing homeostatic EMT in lung cancer cells. Loss of ARID1A, DOT1L, BRD2, and ZMYND8 had nondeterministic and sometimes opposite consequences on epithelial-mesenchymal interconversion. Together with RNAPII and AP-1, these antagonistic gatekeepers control chromatin of active enhancers, including pan-cancer-EMT signature genes enabling supraclassification of anatomically diverse tumors. Thus, our data uncover general principles underlying transcriptional control of cancer cell plasticity and offer a platform to systematically explore chromatin regulators in tumor-state–specific therapy.

scholarly journals Upregulation of LINC01426 promotes the progression and stemness in lung adenocarcinoma by enhancing the level of SHH protein to activate the hedgehog pathway

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Xiaoli Liu ◽  
Zuwei Yin ◽  
Linping Xu ◽  
Huaimin Liu ◽  
Lifeng Jiang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Bioinformatics Analysis ◽  
Epithelial Mesenchymal Transition ◽  
Mrna Level ◽  
Hedgehog Pathway ◽  
Biological Processes ◽  
Protein Coding ◽  
Mesenchymal Transition ◽  
Functional Roles ◽  
Rip Assay

AbstractLong noncoding RNAs (lncRNAs) play crucial roles in regulating a variety of biological processes in lung adenocarcinoma (LUAD). In our study, we mainly explored the functional roles of a novel lncRNA long intergenic non-protein coding RNA 1426 (LINC01426) in LUAD. We applied bioinformatics analysis to find the expression of LINC01426 was upregulated in LUAD tissue. Functionally, silencing of LINC01426 obviously suppressed the proliferation, migration, epithelial–mesenchymal transition (EMT), and stemness of LUAD cells. Then, we observed that LINC01426 functioned through the hedgehog pathway in LUAD. The effect of LINC01426 knockdown could be fully reversed by adding hedgehog pathway activator SAG. In addition, we proved that LINC01426 could not affect SHH transcription and its mRNA level. Pull-down sliver staining and RIP assay revealed that LINC01426 could interact with USP22. Ubiquitination assays manifested that LINC01426 and USP22 modulated SHH ubiquitination levels. Rescue assays verified that SHH overexpression rescued the cell growth, migration, and stemness suppressed by LINC01426 silencing. In conclusion, LINC01426 promotes LUAD progression by recruiting USP22 to stabilize SHH protein and thus activate the hedgehog pathway.

scholarly journals The Epithelial–Mesenchymal Transcription Factor SNAI1 Represses Transcription of the Tumor Suppressor miRNA let-7 in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1469
Author(s):  
Hanmin Wang ◽  
Evgeny Chirshev ◽  
Nozomi Hojo ◽  
Tise Suzuki ◽  
Antonella Bertucci ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cell ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Burden ◽  
Cell Phenotype ◽  
Mesenchymal Transition ◽  
Carcinoma Cell Lines ◽  
Future Work

We aimed to determine the mechanism of epithelial–mesenchymal transition (EMT)-induced stemness in cancer cells. Cancer relapse and metastasis are caused by rare stem-like cells within tumors. Studies of stem cell reprogramming have linked let-7 repression and acquisition of stemness with the EMT factor, SNAI1. The mechanisms for the loss of let-7 in cancer cells are incompletely understood. In four carcinoma cell lines from breast cancer, pancreatic cancer, and ovarian cancer and in ovarian cancer patient-derived cells, we analyzed stem cell phenotype and tumor growth via mRNA, miRNA, and protein expression, spheroid formation, and growth in patient-derived xenografts. We show that treatment with EMT-promoting growth factors or SNAI1 overexpression increased stemness and reduced let-7 expression, while SNAI1 knockdown reduced stemness and restored let-7 expression. Rescue experiments demonstrate that the pro-stemness effects of SNAI1 are mediated via let-7. In vivo, nanoparticle-delivered siRNA successfully knocked down SNAI1 in orthotopic patient-derived xenografts, accompanied by reduced stemness and increased let-7 expression, and reduced tumor burden. Chromatin immunoprecipitation demonstrated that SNAI1 binds the promoters of various let-7 family members, and luciferase assays revealed that SNAI1 represses let-7 transcription. In conclusion, the SNAI1/let-7 axis is an important component of stemness pathways in cancer cells, and this study provides a rationale for future work examining this axis as a potential target for cancer stem cell-specific therapies.

scholarly journals Associations between the Epithelial-Mesenchymal Transition Phenotypes of Circulating Tumor Cells and the Clinicopathological Features of Patients with Colorectal Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Fengjie Wu ◽  
Jun Zhu ◽  
Yongjiang Mao ◽  
Xiaomei Li ◽  
Baoguang Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Peripheral Blood ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Cell ◽  
Blood Samples ◽  
Mesenchymal Transition ◽  
Enrichment Technique ◽  
Tumor Node Metastasis Stage ◽  
Mesenchymal Cell Marker ◽  
Circulating Tumor Microemboli

In this study, we identified CTCs using the previously reported CanPatrol CTC enrichment technique from peripheral blood samples of 126 patients with colorectal cancer (CRC) and found that CTCs could be classified into three subpopulations based on expression of epithelial cell adhesion molecule (EpCAM) (E-CTCs), the mesenchymal cell marker vimentin (M-CTCs), or both EpCAM and vimentin (biphenotypic E/M-CTCs). Circulating tumor microemboli (CTMs) were also identified in peripheral blood samples. Meanwhile, E-CTCs, M-CTCs, E/M-CTCs, and CTMs were detected in 76.98%, 42.06%, 56.35%, and 36.51% of the 126 patients, respectively. Interestingly, the presence of CTMs and each CTC subpopulation was significantly associated with blood lymphocyte counts and tumor-node-metastasis stage (P<0.001). Lymphocyte counts and the neutrophil-to-lymphocyte ratio (NLR) in patients lacking CTCs were significantly different from those in patients testing positive for CTMs and each CTC subpopulation (P<0.001). Our results indicate that tumor metastasis is more significantly associated with the presence of CTMs and M-CTCs than with other CTC subpopulations and suggest that EMT may be involved in CTC evasion of lymphocyte-mediated clearance.

Riboregulators in plant development

2007 ◽  
Vol 35 (6) ◽  
pp. 1638-1642 ◽  
Author(s):  
P. Laporte ◽  
F. Merchan ◽  
B.B. Amor ◽  
S. Wirth ◽  
M. Crespi
Keyword(s):  
Large Scale ◽  
Transcriptional Control ◽  
Rna Binding ◽  
Bioinformatic Analysis ◽  
Nodule Development ◽  
Small Interfering Rnas ◽  
Cortical Cells ◽  
Protein Coding ◽  
Early Nodulin ◽  
Model Plant Arabidopsis Thaliana

npcRNA (non-protein-coding RNAs) are an emerging class of regulators, so-called riboregulators, and include a large diversity of small RNAs [miRNAs (microRNAs)/siRNAs (small interfering RNAs)] that are involved in various developmental processes in plants and animals. In addition, several other npcRNAs encompassing various transcript sizes (up to several kilobases) have been identified using different genomic approaches. Much less is known about the mechanism of action of these other classes of riboregulators also present in the cell. The organogenesis of nitrogen-fixing nodules in legume plants is initiated in specific root cortical cells that express the npcRNA MtENOD40 (Medicago truncatula early nodulin 40). We have identified a novel RBP (RNA-binding protein), MtRBP1 (M. truncatula RBP 1), which interacts with the MtENOD40 RNA, and is exported into the cytoplasm during legume nodule development in the region expressing MtENOD40. A direct involvement of the MtENOD40 RNA in the relocalization of this RBP into cytoplasmic granules could be demonstrated, revealing a new RNA function in the cell. To extend these results, we searched for npcRNAs in the model plant Arabidopsis thaliana whose genome is completely known. We have identified 86 novel npcRNAs from which 27 corresponded to antisense RNAs of known coding regions. Using a dedicated ‘macroarray’ containing these npcRNAs and a collection of RBPs, we characterized their regulation in different tissues and plants subjected to environmental stresses. Most of the npcRNAs showed high variations in gene expression in contrast with the RBP genes. Recent large-scale analysis of the sRNA component of the transcriptome revealed an enormous diversity of siRNAs/miRNAs in the Arabidopsis genome. Bioinformatic analysis revealed that 34 large npcRNAs are precursors of siRNAs/miRNAs. npcRNAs, which are a sensitive component of the transcriptome, may reveal novel riboregulatory mechanisms involved in post-transcriptional control of differentiation or environmental responses.

scholarly journals FEZF1-AS1: a novel vital oncogenic lncRNA in multiple human malignancies

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Changlong Shi ◽  
Li Sun ◽  
Yongsheng Song
Keyword(s):  
Transcriptional Activation ◽  
Epithelial Mesenchymal Transition ◽  
Chromatin Modification ◽  
Research Progress ◽  
Organ Specificity ◽  
Signal Pathways ◽  
Protein Coding ◽  
Mesenchymal Transition ◽  
Regulatory Processes ◽  
Transcription 3

AbstractLong noncoding RNAs (LncRNAs) refer to the RNA with a length of >200 nucleotides, which lack or have no open reading coding frame and have higher tissue and organ specificity compared with the protein coding genes. A surging number of studies have shown that lncRNA is involved in numerous essential regulatory processes, such as X chromosome silencing, genomic imprinting, chromatin modification, transcriptional activation, transcriptional interference and nuclear transport, which are closely related to the occurrence and development of human malignancies. FEZ family Zinc Finger 1-Antisense RNA 1 (FEZF1-AS1) of FEZ family is a recently discovered lncRNA. FEZF1-AS1 is highly expressed in pancreatic cancer, colorectal cancer, lung adenocarcinoma and other human malignancies, and is associated with poor prognosis. As an oncogene, it plays crucial role in the proliferation, migration, invasion and Warburg effect of various tumor cells. In addition, FEZF1-AS1 is also involved in the regulation of multiple signal pathways such as epithelial–mesenchymal transition (EMT), signal transducer and activator of transcription 3 (STAT3) and Wnt/ β-catenin. In this paper, the recent research progress of FEZF1-AS1 in tumorigenesis and development is reviewed systematically.

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