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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Tumor suppressive microRNA-200a inhibits renal cell carcinoma development by directly targeting TGFB2
Ruijing Lu,Ziliang Ji,Xiaoqing Li,Jie Qin,Guanghui Cui,Jing Chen,Qingna Zhai,Chunjuan Zhao,Wei Zhang,Zhendong Yu +9 more
TL;DR: It is reported that the expression of miR-200a was notably downregulated in 45 renal cell carcinoma (RCC) samples, and siRNA-mediated knockdown of TGFB2 partially phenocopied the effect ofmiR- 200a overexpression, suggesting that miR -200a may present a novel target for diagnostic and therapeutic strategies in RCC.
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Cancer Stemness: p53 at the Wheel.
TL;DR: In this article, the role of wild type p53 in regulating pluripotency of normal stem cells and various mechanisms that control the balance between self-renewal and differentiation in embryonic and adult stem cells.
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Tissue-based identification of stem cells and epithelial-to-mesenchymal transition in breast cancer.
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TL;DR: Identifying stem cells and cells undergoing epithelial-to-mesenchymal transition in breast tissue samples would enable pathologists to discover and validate prognostic and predictive markers as well as identify markers of increased risk for breast cancer.
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Antitumor efficacy of viable tumor vaccine modified by heterogenetic ESAT-6 antigen and cytokine IL-21 in melanomatous mouse
Xiangfeng He,Jing Wang,Fengshu Zhao,Fangliu Yu,Dengyu Chen,Kai Cai,Cuiping Yang,Junsong Chen,Jun Dou +8 more
TL;DR: Findings highlighted IL-21 as an immune adjuvant in an engineered viable tumor vaccine to reinforce heterogenetic antigen ESAT-6 immune tolerance break to induce powerful antitumor efficacy in mice.
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Identification of epidermal growth factor receptor and its inhibitory microRNA141 as novel targets of Krüppel-like factor 8 in breast cancer.
TL;DR: A novel KLF8 to miR141/EGFR signaling pathway potentially crucial for breast cancer malignancy is reported, demonstrating a highly correlated co-overexpression between KLf8 and EGFR in invasive breast cancer cells and patient tumor samples.
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