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 induced miR-99b/let-7e/miR-125a cluster promotes invasion and metastasis in esophageal squamous cell carcinoma.
Jianlin Ma,Yun Zhan,Zhipeng Xu,Yi Li,Aiping Luo,Fang Ding,Xiu-Feng Cao,Hongyan Chen,Zhihua Liu +8 more
TL;DR: Light is shed on the essential role of miR-99b/let-7e/miR-125a cluster in tumor metastasis by identifying this miRNA cluster as pro-metastasis oncomir.
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microRNA-200b modulates microglia-mediated neuroinflammation via the cJun/MAPK pathway
TL;DR: Results indicate that miRNA‐200b modulates microglial inflammatory process including cytokine secretion, NO production, migration and neuronal survival.
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lncRNA PVT1 and its splicing variant function as competing endogenous RNA to regulate clear cell renal cell carcinoma progression
Tao Yang,Tao Yang,Hui Zhou,Peijun Liu,Libin Yan,Weimin Yao,Ke Chen,Jin Zeng,Heng Li,Junhui Hu,Hua Xu,Zhangqun Ye +11 more
TL;DR: Mechanistic investigations indicated that PVT1ΔE4 could also upregulate the expression of BMI1, ZEB1 and ZEB2 through interacting with miR-200s and this study helps reveal new molecular events in ccRCC and provides promising diagnostic and therapeutic targets for this disease.
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MicroRNAs in Diabetic Kidney Disease
TL;DR: Functional studies indicate that the ability of microRNAs to bind 3′ untranslated region of messenger RNA not only shows their capability to regulate expression of target genes, but also their therapeutic potential to diabetic kidney disease.
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Molecular regulation of Snai2 in development and disease.
TL;DR: Current understanding of the molecular mechanisms regulating Snai2 (Slug) expression, abundance and activity are discussed, outlining how these contribute to disease phenotypes or may impact therapeutic targeting of Snai1 dysregulation in human disease.
References
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Journal Article
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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
TL;DR: A mechanistic link between Twist, EMT, and tumor metastasis is established, suggesting that Twist contributes to metastasis by promoting an epithelial-mesenchymal transition (EMT).