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...
Main Authors: | , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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BMC
2019-03-01
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Series: | Journal of Experimental & Clinical Cancer Research |
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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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issn | 1756-9966 |
language | English |
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publishDate | 2019-03-01 |
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series | Journal of Experimental & Clinical Cancer Research |
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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