Please use this identifier to cite or link to this item: 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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