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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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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Loss of miR-200 Inhibition of Suz12 Leads to Polycomb-Mediated Repression Required for the Formation and Maintenance of Cancer Stem Cells
Dimitrios Iliopoulos,Marianne Lindahl-Allen,Christos Polytarchou,Heather A. Hirsch,Philip N. Tsichlis,Kevin Struhl +5 more
TL;DR: The interaction between miR-200 and Suz12 is highly conserved, suggesting that it represents an ancient regulatory mechanism to control the growth and function of stem cells.
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Coordinated epigenetic repression of the miR‐200 family and miR‐205 in invasive bladder cancer
Erik D Wiklund,Jesper B. Bramsen,Toby Hulf,Lars Dyrskjøt,Ramshanker Ramanathan,Thomas B. Hansen,Sune B. Villadsen,Shan Gao,Marie Stampe Ostenfeld,Michael Borre,Marcus E. Peter,Torben F. Ørntoft,Jørgen Kjems,Susan J. Clark +13 more
TL;DR: It is shown that themiR‐200 and miR‐205 loci are specifically silenced and gain promoter hypermethylation and repressive chromatin marks in muscle invasive bladder tumors and undifferentiated bladder cell lines, and it is proposed that miR200c expression is significantly correlated with early stage T1 bladder tumor progression.
Journal ArticleDOI
Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let‐7
Surabhi Dangi-Garimella,Jieun Yun,Eva M. Eves,Martin A. Newman,Stefan J. Erkeland,Scott M. Hammond,Andy J. Minn,Marsha Rich Rosner +7 more
TL;DR: RKIP regulation of two pluripotent stem cell genes, Myc and LIN28, highlights the importance of RKIP as a key metastasis suppressor and potential therapeutic agent.
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MicroRNAs Are Absorbed in Biologically Meaningful Amounts from Nutritionally Relevant Doses of Cow Milk and Affect Gene Expression in Peripheral Blood Mononuclear Cells, HEK-293 Kidney Cell Cultures, and Mouse Livers
TL;DR: It is concluded that miRNAs in milk are bioactive food compounds that regulate human genes.
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MicroRNAs in colorectal cancer: translation of molecular biology into clinical application
TL;DR: The knowledge regarding miRNAs' functioning in CRC is summarized while emphasizing their significance in pathogenetic signaling pathways and their potential to serve as disease biomarkers and novel therapeutic targets.
References
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