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Long non-coding RNA ZEB1-AS1 regulates miR-200b/FSCN1 signaling and enhances migration and invasion induced by TGF-β1 in bladder cancer cells
BACKGROUND: The effect of competing endogenous RNA (ceRNA) can regulate gene expression by competitively binding microRNAs. Fascin-1 (FSCN1) plays an important role in the regulation of cellular migration and invasion during tumor progression, but how its regulatory mechanism works through the ceRNA...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397446/ https://www.ncbi.nlm.nih.gov/pubmed/30823924 http://dx.doi.org/10.1186/s13046-019-1102-6 |
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author | Gao, Ruxu Zhang, Naiwen Yang, Jianyu Zhu, Yuyan Zhang, Zhe Wang, Jianfeng Xu, Xiaolong Li, Zeliang Liu, Xiankui Li, Zhenhua Li, Jun Kong, Chuize Bi, Jianbin |
author_facet | Gao, Ruxu Zhang, Naiwen Yang, Jianyu Zhu, Yuyan Zhang, Zhe Wang, Jianfeng Xu, Xiaolong Li, Zeliang Liu, Xiankui Li, Zhenhua Li, Jun Kong, Chuize Bi, Jianbin |
author_sort | Gao, Ruxu |
collection | PubMed |
description | BACKGROUND: The effect of competing endogenous RNA (ceRNA) can regulate gene expression by competitively binding microRNAs. Fascin-1 (FSCN1) plays an important role in the regulation of cellular migration and invasion during tumor progression, but how its regulatory mechanism works through the ceRNA effect is still unclear in bladder cancer (BLCA). METHODS: The role of fascin-1, miR-200b, and ZEB1-AS1 in BLCA was investigated in vitro and in vivo. The interaction between fascin-1, miR-200b, and ZEB1-AS1 was identified using bioinformatics analysis, luciferase activity assays, RNA-binding protein immunoprecipitation (RIP), quantitative PCR, and western blotting. Loss (or gain)-of-function experiments were performed to investigate the biological roles of miR-200b and ZEB1-AS1 on migration, invasion, proliferation, cell apoptosis, and cell cycle. RESULTS: ZEB1-AS1 functions as a competing endogenous RNA in BLCA to regulate the expression of fascin-1 through miR-200b. Moreover, the oncogenic long non-coding RNA ZEB1-AS1 was highly expressed in BLCA and positively correlated with high tumor grade, high TNM stage, and reduced survival of patients with BLCA. Moreover, ZEB1-AS1 downregulated the expression of miR-200b, promoted migration, invasion, and proliferation, and inhibited apoptosis in BLCA. Furthermore, we found TGF-β1 induced migration and invasion in BLCA by regulating the ZEB1-AS1/miR-200b/FSCN1 axis. CONCLUSION: The observations in this study identify an important regulatory mechanism of fascin-1 in BLCA, and the TGF-β1/ZEB1-AS1/miR-200b/FSCN1 axis may serve as a potential target for cancer therapeutic purposes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-019-1102-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6397446 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-63974462019-03-13 Long non-coding RNA ZEB1-AS1 regulates miR-200b/FSCN1 signaling and enhances migration and invasion induced by TGF-β1 in bladder cancer cells Gao, Ruxu Zhang, Naiwen Yang, Jianyu Zhu, Yuyan Zhang, Zhe Wang, Jianfeng Xu, Xiaolong Li, Zeliang Liu, Xiankui Li, Zhenhua Li, Jun Kong, Chuize Bi, Jianbin J Exp Clin Cancer Res Research BACKGROUND: The effect of competing endogenous RNA (ceRNA) can regulate gene expression by competitively binding microRNAs. Fascin-1 (FSCN1) plays an important role in the regulation of cellular migration and invasion during tumor progression, but how its regulatory mechanism works through the ceRNA effect is still unclear in bladder cancer (BLCA). METHODS: The role of fascin-1, miR-200b, and ZEB1-AS1 in BLCA was investigated in vitro and in vivo. The interaction between fascin-1, miR-200b, and ZEB1-AS1 was identified using bioinformatics analysis, luciferase activity assays, RNA-binding protein immunoprecipitation (RIP), quantitative PCR, and western blotting. Loss (or gain)-of-function experiments were performed to investigate the biological roles of miR-200b and ZEB1-AS1 on migration, invasion, proliferation, cell apoptosis, and cell cycle. RESULTS: ZEB1-AS1 functions as a competing endogenous RNA in BLCA to regulate the expression of fascin-1 through miR-200b. Moreover, the oncogenic long non-coding RNA ZEB1-AS1 was highly expressed in BLCA and positively correlated with high tumor grade, high TNM stage, and reduced survival of patients with BLCA. Moreover, ZEB1-AS1 downregulated the expression of miR-200b, promoted migration, invasion, and proliferation, and inhibited apoptosis in BLCA. Furthermore, we found TGF-β1 induced migration and invasion in BLCA by regulating the ZEB1-AS1/miR-200b/FSCN1 axis. CONCLUSION: The observations in this study identify an important regulatory mechanism of fascin-1 in BLCA, and the TGF-β1/ZEB1-AS1/miR-200b/FSCN1 axis may serve as a potential target for cancer therapeutic purposes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-019-1102-6) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-01 /pmc/articles/PMC6397446/ /pubmed/30823924 http://dx.doi.org/10.1186/s13046-019-1102-6 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Gao, Ruxu Zhang, Naiwen Yang, Jianyu Zhu, Yuyan Zhang, Zhe Wang, Jianfeng Xu, Xiaolong Li, Zeliang Liu, Xiankui Li, Zhenhua Li, Jun Kong, Chuize Bi, Jianbin Long non-coding RNA ZEB1-AS1 regulates miR-200b/FSCN1 signaling and enhances migration and invasion induced by TGF-β1 in bladder cancer cells |
title | Long non-coding RNA ZEB1-AS1 regulates miR-200b/FSCN1 signaling and enhances migration and invasion induced by TGF-β1 in bladder cancer cells |
title_full | Long non-coding RNA ZEB1-AS1 regulates miR-200b/FSCN1 signaling and enhances migration and invasion induced by TGF-β1 in bladder cancer cells |
title_fullStr | Long non-coding RNA ZEB1-AS1 regulates miR-200b/FSCN1 signaling and enhances migration and invasion induced by TGF-β1 in bladder cancer cells |
title_full_unstemmed | Long non-coding RNA ZEB1-AS1 regulates miR-200b/FSCN1 signaling and enhances migration and invasion induced by TGF-β1 in bladder cancer cells |
title_short | Long non-coding RNA ZEB1-AS1 regulates miR-200b/FSCN1 signaling and enhances migration and invasion induced by TGF-β1 in bladder cancer cells |
title_sort | long non-coding rna zeb1-as1 regulates mir-200b/fscn1 signaling and enhances migration and invasion induced by tgf-β1 in bladder cancer cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6397446/ https://www.ncbi.nlm.nih.gov/pubmed/30823924 http://dx.doi.org/10.1186/s13046-019-1102-6 |
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