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https://hdl.handle.net/11499/30115
Title: | TGF-ß-SMAD-miR-520e axis regulates NSCLC metastasis through a TGFBR2-mediated negative-feedback loop | Authors: | Küçüksayan, Hakan Akgun, S. Ozes, O.N. Alikanoglu, A.S. Yildiz, M. Dal, Egemen Akça, Hakan |
Keywords: | biological marker microRNA microRNA 520e Smad protein transforming growth factor beta transforming growth factor beta receptor 2 unclassified drug MIRN520 microRNA, human Smad2 protein SMAD2 protein, human Smad3 protein SMAD3 protein, human TGFB1 protein, human TGFBR2 protein, human transforming growth factor beta1 tumor marker A-549 cell line Article cancer inhibition carcinogenesis chromatin immunoprecipitation gene expression gene induction human human cell human cell culture luciferase assay metastasis MTT assay negative feedback non small cell lung cancer polymerase chain reaction priority journal RNA isolation apoptosis cell motion cell proliferation gene expression regulation genetics lung tumor lymph node metastasis metabolism pathology physiological feedback signal transduction tumor invasion A549 Cells Apoptosis Biomarkers, Tumor Carcinoma, Non-Small-Cell Lung Cell Movement Cell Proliferation Feedback, Physiological Gene Expression Regulation, Neoplastic Humans Lung Neoplasms Lymphatic Metastasis MicroRNAs Neoplasm Invasiveness Receptor, Transforming Growth Factor-beta Type II Signal Transduction Smad2 Protein Smad3 Protein Transforming Growth Factor beta1 |
Publisher: | Oxford University Press | Abstract: | Transforming growth factor-ß (TGF-ß) pathway plays crucial roles during the carcinogenesis and metastasis. TGF-ß receptor 2 (TGFBR2) is a key molecule for the regulation of TGF-ß pathway and frequently downregulated or lost in several cancer types including non-small cell lung cancer (NSCLC), and TGF-ß pathway is often regulated by negative-feedback mechanisms, but little is known about the mechanism of TGFBR2 downregulation in NSCLC. Here, we found that the expression of miR-520e is upregulated in metastatic tumor tissues compared with non-metastatic ones, and its expression is inversely correlated with that of TGFBR2 in clinical samples. We also discovered that TGF-ß dramatically increased the expression of miR-520e, which targeted and downregulated TGFBR2, and the suppression of miR-520e significantly impaired TGF-ß-induced TGFBR2 downregulation. Chromatin immunoprecipitation-PCR experiments further showed that miR-520e is transcriptionally induced by SMAD2/3 in response to TGF-ß. Our findings reveal a novel negative-feedback mechanism in TGF-ß signaling and the expression level of miR-520e could be a predictive biomarker for NSCLC metastasis. © 2018 The Author(s) 2018. Published by Oxford University Press. All rights reserved. | URI: | https://hdl.handle.net/11499/30115 https://doi.org/10.1093/carcin/bgy166 |
ISSN: | 0143-3334 |
Appears in Collections: | PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection Tıp Fakültesi Koleksiyonu WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection |
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