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A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells

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TLDR
Results indicate that ZEB1 triggers an microRNA‐mediated feedforward loop that stabilizes EMT and promotes invasion of cancer cells, and thus explain the strong intratumorous heterogeneity observed in many human cancers.
Abstract
The embryonic programme 'epithelial-mesenchymal transition' (EMT) is thought to promote malignant tumour progression. The transcriptional repressor zinc-finger E-box binding homeobox 1 (ZEB1) is a crucial inducer of EMT in various human tumours, and was recently shown to promote invasion and metastasis of tumour cells. Here, we report that ZEB1 directly suppresses transcription of microRNA-200 family members miR-141 and miR-200c, which strongly activate epithelial differentiation in pancreatic, colorectal and breast cancer cells. Notably, the EMT activators transforming growth factor beta2 and ZEB1 are the predominant targets downregulated by these microRNAs. These results indicate that ZEB1 triggers an microRNA-mediated feedforward loop that stabilizes EMT and promotes invasion of cancer cells. Alternatively, depending on the environmental trigger, this loop might switch and induce epithelial differentiation, and thus explain the strong intratumorous heterogeneity observed in many human cancers.

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Journal ArticleDOI

Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through

TL;DR: The miR-200c/141 transcription is intimately linked to the transcription of the proximal upstream gene PTPN6 (SHP1) in all physiological conditions tested and highlights that transcription of intergenic miRNAs is a novel outcome of transcriptional read-through.
Journal ArticleDOI

Epigenetic regulators of programmed death-ligand 1 expression in human cancers.

TL;DR: Recent findings and evidence on epigenetic mechanisms that regulate PD‐L1 expression and the biological and clinical implications of such regulation in cancer are reviewed.
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Radiogenomic Analysis Demonstrates Associations between (18)F-Fluoro-2-Deoxyglucose PET, Prognosis, and Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer.

TL;DR: Investigating whether non-small cell lung cancer tumors that express high normalized maximum standardized uptake value (SUVmax) are associated with a more epithelial-mesenchymal transition (EMT)-like phenotype demonstrates an association between increased normalized fluoro-2-deoxyglucose PET SUVmax, outcome, and EMT in NSCLC.
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Epithelial–mesenchymal transition in Crohn’s disease

TL;DR: Current knowledge of epithelial–mesenchymal transition and its role in the pathogenesis of CD is presented in order to highlight new therapy targets for the associated complications.
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Lung cancer and miRNAs: a possible remedy for anti-metastatic, therapeutic and diagnostic applications

TL;DR: The recent advances made in the understanding of the miRNAs with special reference to lung cancer are summarized and different kinds of them would be discussed to delineate their significance in lung cancer biology, therapy and diagnosis.
References
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Journal ArticleDOI

MicroRNAs: Genomics, Biogenesis, Mechanism, and Function

TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
Journal Article

Oncomirs : microRNAs with a role in cancer

TL;DR: I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators as discussed by the authors, and have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.
Journal ArticleDOI

Prediction of Mammalian MicroRNA Targets

TL;DR: The predicted regulatory targets of mammalian miRNAs were enriched for genes involved in transcriptional regulation but also encompassed an unexpectedly broad range of other functions.
Journal ArticleDOI

Complex networks orchestrate epithelial–mesenchymal transitions

TL;DR: Understanding how mesenchymal cells arise from an epithelial default status will also have a strong impact in unravelling the mechanisms that control fibrosis and cancer progression.
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