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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ZEB1 in Pancreatic Cancer.
TL;DR: The biological functions of ZEB1 are reviewed with a focus on pancreatic cancer, with experimental support for the migrating cancer stem cell (MCSC) hypothesis.
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Integrated genomics of chemotherapy resistant ovarian cancer: A role for extracellular matrix, TGFbeta and regulating microRNAs
Jozien Helleman,Maurice P.H.M. Jansen,Curt W. Burger,Maria E. L. van der Burg,Els M.J.J. Berns +4 more
TL;DR: A model is presented based on literature linking transforming growth factor beta, extracellular matrix, integrin signalling, epithelial to mesenchymal transition and regulating microRNAs with a (bivalent) role in chemotherapy response.
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MicroRNAs and the glomerulus
TL;DR: The biogenesis of miRNAs and their functions in the glomerulus are summarized, with particular emphasis on glomerular mesangial cells and podocytes related to the pathogenesis of DN.
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Protective effects of miR-29a on diabetic glomerular dysfunction by modulation of DKK1/Wnt/β-catenin signaling.
Yung-Chien Hsu,Pey-Jium Chang,Cheng Ho,Yu-Ting Huang,Ya-Hsueh Shih,Ching-Jen Wang,Chun-Liang Lin +6 more
TL;DR: The findings suggest that the reciprocal relationship between miR-29a and DKK1/Wnt/β-catenin signaling may play an important part in protecting renal fibrogenesis.
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microRNA-200a Inhibits Cell Proliferation by Targeting Mitochondrial Transcription Factor A in Breast Cancer
TL;DR: Findings will shed light on the role and mechanism of miR-200a in regulating BC cells growth and mtDNA copy number via miR,200a/TFAM axis, and miR -200a may serve as a potential therapeutic target in BC in the future.
References
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Twist, a Master Regulator of Morphogenesis, Plays an Essential Role in Tumor Metastasis
Jing Yang,Sendurai A. Mani,Joana Liu Donaher,Sridhar Ramaswamy,Sridhar Ramaswamy,Raphael Itzykson,Christophe Côme,Pierre Savagner,Inna Gitelman,Andrea L. Richardson,Robert A. Weinberg +10 more
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