Long non-coding RNA ZEB1-AS1 regulates miR-200b/FSCN1 signaling and enhances migration and invasion induced by TGF-β1 in bladder cancer cells

Abstract 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 t...

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Main Authors: Ruxu Gao, Naiwen Zhang, Jianyu Yang, Yuyan Zhu, Zhe Zhang, Jianfeng Wang, Xiaolong Xu, Zeliang Li, Xiankui Liu, Zhenhua Li, Jun Li, Chuize Kong, Jianbin Bi
Format: Article
Language:English
Published: BMC 2019-03-01
Series:Journal of Experimental & Clinical Cancer Research
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13046-019-1102-6
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author Ruxu Gao
Naiwen Zhang
Jianyu Yang
Yuyan Zhu
Zhe Zhang
Jianfeng Wang
Xiaolong Xu
Zeliang Li
Xiankui Liu
Zhenhua Li
Jun Li
Chuize Kong
Jianbin Bi
author_facet Ruxu Gao
Naiwen Zhang
Jianyu Yang
Yuyan Zhu
Zhe Zhang
Jianfeng Wang
Xiaolong Xu
Zeliang Li
Xiankui Liu
Zhenhua Li
Jun Li
Chuize Kong
Jianbin Bi
author_sort Ruxu Gao
collection DOAJ
description Abstract 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.
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spelling doaj.art-95f6303b9b0643fb8a9c4acb9286c8952022-12-22T03:04:59ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-03-0138111510.1186/s13046-019-1102-6Long non-coding RNA ZEB1-AS1 regulates miR-200b/FSCN1 signaling and enhances migration and invasion induced by TGF-β1 in bladder cancer cellsRuxu Gao0Naiwen Zhang1Jianyu Yang2Yuyan Zhu3Zhe Zhang4Jianfeng Wang5Xiaolong Xu6Zeliang Li7Xiankui Liu8Zhenhua Li9Jun Li10Chuize Kong11Jianbin Bi12Department of Urology, The First Hospital of China Medical UniversityDepartment of Urology, The First Hospital of China Medical UniversityDepartment of Urology, The First Hospital of China Medical UniversityDepartment of Urology, The First Hospital of China Medical UniversityDepartment of Urology, The First Hospital of China Medical UniversityDepartment of Urology, The First Hospital of China Medical UniversityDepartment of Urology, The First Hospital of China Medical UniversityDepartment of Urology, The First Hospital of China Medical UniversityDepartment of Urology, The First Hospital of China Medical UniversityDepartment of Urology, The First Hospital of China Medical UniversityDepartment of Urology, The First Hospital of China Medical UniversityDepartment of Urology, The First Hospital of China Medical UniversityDepartment of Urology, The First Hospital of China Medical UniversityAbstract 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.http://link.springer.com/article/10.1186/s13046-019-1102-6Bladder cancerfascin1Long non-coding RNA ZEB1-AS1microRNA miR-200bTGF-β1
spellingShingle Ruxu Gao
Naiwen Zhang
Jianyu Yang
Yuyan Zhu
Zhe Zhang
Jianfeng Wang
Xiaolong Xu
Zeliang Li
Xiankui Liu
Zhenhua Li
Jun Li
Chuize Kong
Jianbin Bi
Long non-coding RNA ZEB1-AS1 regulates miR-200b/FSCN1 signaling and enhances migration and invasion induced by TGF-β1 in bladder cancer cells
Journal of Experimental & Clinical Cancer Research
Bladder cancer
fascin1
Long non-coding RNA ZEB1-AS1
microRNA miR-200b
TGF-β1
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 Bladder cancer
fascin1
Long non-coding RNA ZEB1-AS1
microRNA miR-200b
TGF-β1
url http://link.springer.com/article/10.1186/s13046-019-1102-6
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