A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells
Ulrike Burk,Joerg Schubert,Ulrich F. Wellner,Otto Schmalhofer,Elizabeth Vincan,Simone Spaderna,Thomas Brabletz +6 more
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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.read more
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Epigenetically Deregulated microRNA-375 Is Involved in a Positive Feedback Loop with Estrogen Receptor α in Breast Cancer Cells
Pedro de Souza Rocha Simonini,Pedro de Souza Rocha Simonini,Achim Breiling,Nibedita Gupta,Mahdi Malekpour,Mahmoud Youns,Mahmoud Youns,Ramesh Omranipour,Fatemeh Malekpour,Stefano Volinia,Carlo M. Croce,Hossein Najmabadi,Sven Diederichs,Ozgur Sahin,Doris Mayer,Frank Lyko,Jörg D. Hoheisel,Yasser Riazalhosseini +17 more
TL;DR: It is shown that high expression of the microRNA miR-375 in ERα-positive breast cell lines is a key driver of their proliferation, and a forward feedback pathway in control of ERα expression is defined, highlighting new strategies to treat ER α-positive invasive breast tumors.
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miR-200a Regulates SIRT1 Expression and Epithelial to Mesenchymal Transition (EMT)-like Transformation in Mammary Epithelial Cells
TL;DR: It is demonstrated that the class III histone deacetylase silent information regulator 1 (SIRT1), a proposed oncogene in breast cancer, is overexpressed upon EMT-like transformation and that epigenetic silencing of miR-200a contributes at least in part to the overexpression of SIRT1.
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The Regulatory Role of MicroRNAs in EMT and Cancer
TL;DR: The most recent advances regarding the influence of miRNAs in EMT and the control they exert in major signaling pathways in various cancers are described.
Journal ArticleDOI
miR-21 and miR-31 Converge on TIAM1 to Regulate Migration and Invasion of Colon Carcinoma Cells
TL;DR: MiR-21 and miR-31 are uncovered as downstream effectors of TGF-β in facilitating invasion and metastasis of colon carcinoma cells in LIM 1863 cells, and there is compelling evidence that TIAM1, a guanidine exchange factor of the Rac GTPase, is a direct target of both miR's.
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Coupled Reversible and Irreversible Bistable Switches Underlying TGFβ-induced Epithelial to Mesenchymal Transition
TL;DR: A mathematical model is constructed for the core regulatory network controlling TGF-β-induced EMT and provides a mechanistic explanation on multiple experimental observations, showing that EMT is a sequential two-step program in which an epithelial cell first is converted to partial EMT then to the mesenchymal state, depending on the strength and duration of T GF-β stimulation.
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