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http://purl.uniprot.org/citations/27383203http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27383203http://www.w3.org/2000/01/rdf-schema#comment"

Background/aims

Transforming growth factor beta (TGF-β) plays a major role in tumorigenesis. MicroRNA-181b (miRNA-181b) is a multifaceted miRNA that has been implicated in many cellular processes such as cell fate determination and cellular invasion. This study aimed to confirm the relationship of miRNA-181b and the TGF-β-Smad2/3/4 pathway with the induction of the epithelial-to-mesenchymal transition (EMT) in gastric cancer.

Methods

This study investigated the ability of TGF-β to induce migration by wound healing and transwell invasion assays in human gastric cancer cell lines. miRNA expression was altered using miRNA-181b mimic and inhibitor in the same system. Expression of miRNA-181b, the hypothetical target gene Timp3 and EMT-related markers were analyzed by real-time real-time quantitative RT-PCR. Immunoblotting was used to investigate the levels of phospho-Smad2 and Smad4. Dual-luciferase reporter assays were performed to confirm the direct binding of miRNA-181b to Timp3.

Results

miRNA-181b was significantly upregulated in response to TGF-β treatment in gastric cancer cell lines. Overexpression of miR-181b mimic induced an in vitro EMT-like change to a phenotype similar to that following TGF-β treatment alone and was reversed by miRNA-181b inhibitor. Inhibition of TGF-β-Smad2/3 signaling with SD-208 significantly attenuated the upregulation of miRNA-181b. Knockdown of Smad4 in gastric cancer cells strongly attenuated the upregulation of miRNA-181b. Moreover, miR-181b was found to directly target the 3' untranslated region (3'UTR) of Timp3 mRNA affecting TGF-β-induced EMT.

Conclusions

Our results elucidate a novel mechanism through which the TGF-β pathway regulates the EMT of gastric cancer cells by increasing the levels of miRNA-181b to target Timp3 via the Smad2/3/4-dependent pathway. These findings provide insights into the cellular and environmental factors regulating EMT, which may guide future studies on therapeutic strategies targeting these cells."xsd:string
http://purl.uniprot.org/citations/27383203http://purl.org/dc/terms/identifier"doi:10.1159/000445638"xsd:string
http://purl.uniprot.org/citations/27383203http://purl.uniprot.org/core/author"Chen L."xsd:string
http://purl.uniprot.org/citations/27383203http://purl.uniprot.org/core/author"Jiang J."xsd:string
http://purl.uniprot.org/citations/27383203http://purl.uniprot.org/core/author"Yang X."xsd:string
http://purl.uniprot.org/citations/27383203http://purl.uniprot.org/core/author"Xu B."xsd:string
http://purl.uniprot.org/citations/27383203http://purl.uniprot.org/core/author"Zhou Q."xsd:string
http://purl.uniprot.org/citations/27383203http://purl.uniprot.org/core/author"Wu C."xsd:string
http://purl.uniprot.org/citations/27383203http://purl.uniprot.org/core/author"Zheng X."xsd:string
http://purl.uniprot.org/citations/27383203http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/27383203http://purl.uniprot.org/core/name"Cell Physiol Biochem"xsd:string
http://purl.uniprot.org/citations/27383203http://purl.uniprot.org/core/pages"453-466"xsd:string
http://purl.uniprot.org/citations/27383203http://purl.uniprot.org/core/title"Smad2/3/4 Pathway Contributes to TGF-beta-Induced MiRNA-181b Expression to Promote Gastric Cancer Metastasis by Targeting Timp3."xsd:string
http://purl.uniprot.org/citations/27383203http://purl.uniprot.org/core/volume"39"xsd:string
http://purl.uniprot.org/citations/27383203http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/27383203
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