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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The role of breast cancer stem cells in metastasis and therapeutic implications.
TL;DR: This review summarizes recent data that support the theory of CSCs as the source of metastatic lesions in breast cancer, with a focus on the key role of the microenvironment in the stemness-metastasis link.
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Transforming growth factor-β1-mediated renal fibrosis is dependent on the regulation of transforming growth factor receptor 1 expression by let-7b
Bo Wang,Jay C. Jha,Shinji Hagiwara,Aaron McClelland,Karin Jandeleit-Dahm,Merlin C. Thomas,Mark E. Cooper,Phillip Kantharidis +7 more
TL;DR: Let-7b microRNA represents a potential new target for the treatment of renal fibrosis in diabetic and non-diabetic nephropathy with the upregulation of TGFBR1.
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miR-205 acts as a tumour radiosensitizer by targeting ZEB1 and Ubc13
Peijing Zhang,Li Wang,Cristian Rodriguez-Aguayo,Yuan Yuan,Bisrat G. Debeb,Dahu Chen,Yutong Sun,M. James You,Yongqing Liu,Douglas C. Dean,Wendy A. Woodward,Han Liang,Xianbin Yang,Gabriel Lopez-Berestein,Anil K. Sood,Ye Hu,K. Kian Ang,Junjie Chen,Li Ma +18 more
TL;DR: It is found that miR-205 promotes radiosensitivity and is downregulated in radioresistant subpopulations of breast cancer cells, and that loss of miR -205 is highly associated with poor distant relapse-free survival in breast cancer patients.
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Circulating miR-200c as a diagnostic and prognostic biomarker for gastric cancer
Manuel Valladares-Ayerbes,Margarita Reboredo,Vanessa Medina-Villaamil,Pilar Iglesias-Díaz,Maria J. Lorenzo-Patiño,Mar Haz,Isabel Santamarina,Moisés Blanco,Juan Fernández-Tajes,Maria Quindós,Alberto Carral,Angélica Figueroa,Luis M. Antón-Aparicio,Lourdes Calvo +13 more
TL;DR: It is suggested that increased miR-200c levels are detected in the blood of gastric cancer patients and has the potential to be a predictor of progression and survival.
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Down-regulation of the miRNA-200 family at the invasive front of colorectal cancers with degraded basement membrane indicates EMT is involved in cancer progression.
Emily L. Paterson,Emily L. Paterson,Jan Kazenwadel,Andrew G. Bert,Yeesim Khew-Goodall,Yeesim Khew-Goodall,Andrew Ruszkiewicz,Gregory J. Goodall,Gregory J. Goodall +8 more
TL;DR: Data support the involvement of EMT and mesenchymal-to-epithelial transition (MET) in the metastasis cascade and show that miR-200 is downregulated in the initial stages of stromal invasion but is restored at metastatic sites.
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