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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

An integrative genomic approach identifies p73 and p63 as activators of miR-200 microRNA family transcription

TL;DR: An integrative approach is delineated that can be applied to discover transcriptional regulatory mechanisms in other biological settings where analogous genomic data is available to discover miRNAs regulated by p73 and p63.
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microRNAs and lung cancer: tumors and 22-mers.

TL;DR: Recent advances in the study of miRNAs involved in tumorigenesis are reviewed, focusing on miRNA regulation of genes that have been demonstrated to play critical roles in lung cancer development.
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Cancer of the Pancreas: Molecular Pathways and Current Advancement in Treatment.

TL;DR: The molecular biology of pancreatic cancer, the major signaling pathways regulating Pancreatic cancer EMT and CSCs, and the advancement in current clinical and experimental treatments for pancreaticcancer are reviewed.
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MicroRNAs in breast cancer initiation and progression

TL;DR: The emerging role of microRNAs in the epigenetic regulation of many cellular processes has become recognized in both basic research and translational medicine as an important way that gene expression can be fine-tuned.
Journal ArticleDOI

Cellular MicroRNAs 200b and 429 Regulate the Epstein-Barr Virus Switch between Latency and Lytic Replication

TL;DR: It is concluded that miRNAs 200b and 429 are key regulators via their effects on expression of ZEB1 and ZEB2 of the switch between latent and lytic infection by EBV and, therefore, potential targets for development of new lytic induction therapeutics with which to treat patients with EBV-associated malignancies.
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.
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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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