MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change

Abstract Background RNA binding proteins (RBPs) have been reported to interact with RNAs to regulate gene expression. Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs, which involved in the angiogenesis of tumor. The purpose of this study is to elucidate the potential roles and mole...

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Main Authors: Qianru He, Lini Zhao, Xiaobai Liu, Jian Zheng, Yunhui Liu, Libo Liu, Jun Ma, Heng Cai, Zhen Li, Yixue Xue
Format: Article
Language:English
Published: BMC 2019-01-01
Series:Journal of Experimental & Clinical Cancer Research
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13046-018-0990-1
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author Qianru He
Lini Zhao
Xiaobai Liu
Jian Zheng
Yunhui Liu
Libo Liu
Jun Ma
Heng Cai
Zhen Li
Yixue Xue
author_facet Qianru He
Lini Zhao
Xiaobai Liu
Jian Zheng
Yunhui Liu
Libo Liu
Jun Ma
Heng Cai
Zhen Li
Yixue Xue
author_sort Qianru He
collection DOAJ
description Abstract Background RNA binding proteins (RBPs) have been reported to interact with RNAs to regulate gene expression. Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs, which involved in the angiogenesis of tumor. The purpose of this study is to elucidate the potential roles and molecular mechanisms of MOV10 and circ-DICER1 in regulating the angiogenesis of glioma-exposed endothelial cells (GECs). Methods The expressions of circ-DICER1, miR-103a-3p and miR-382-5p were detected by real-time PCR. The expressions of MOV10, ZIC4, Hsp90 and PI3K/Akt were detected by real-time PCR or western blot. The binding ability of circ-SHKBP1 and miR-544a / miR-379, ZIC4 and miR-544a / miR-379 were analyzed with Dual-Luciferase Reporter System or RIP experiment. The direct effects of ZIC4 on the Hsp90β promoter were analyzed by the ChIP experiment. The cell viability, migration and tube formation in vitro were detected by CCK-8, Transwell assay and Matrigel tube formation assay. The angiogenesis in vivo was evaluated by Matrigel plug assay. Student’s t-test (two tailed) was used for comparisons between two groups. One-way analysis of variance (ANOVA) was used for multi-group comparisons followed by Bonferroni post-hoc analysis. Results The expressions of RNA binding proteins MOV10, circ-DICER1, ZIC4, and Hsp90β were up-regulated in GECs, while miR103a-3p/miR-382-5p were down-regulated. MOV10 binding circ-DICER1 regulated the cell viability, migration, and tube formation of GECs. And the effects of both MOV10 and circ-DICER1 silencing were better than the effects of MOV10 or circ-DICER1 alone silencing. In addition, circ-DICER1 acts as a molecular sponge to adsorb miR-103a-3p / miR-382-5p and impair the negative regulation of miR-103a-3p / miR-382-5p on ZIC4 in GECs. Furthermore, ZIC4 up-regulates the expression of its downstream target Hsp90β, and Hsp90 promotes the cell viability, migration, and tube formation of GECs by activating PI3K/Akt signaling pathway. Conclusions MOV10 / circ-DICER1 / miR-103a-3p (miR-382-5p) / ZIC4 pathway plays a vital role in regulating the angiogenesis of glioma. Our findings not only provides novel mechanisms for the angiogenesis of glioma, but also provide potential targets for anti-angiogenesis therapies of glioma.
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spelling doaj.art-2c1a8c07dfb146cfa282df63ed77614f2022-12-22T01:31:57ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-01-0138111710.1186/s13046-018-0990-1MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression changeQianru He0Lini Zhao1Xiaobai Liu2Jian Zheng3Yunhui Liu4Libo Liu5Jun Ma6Heng Cai7Zhen Li8Yixue Xue9Department of Neurobiology, School of Life Sciences, China Medical UniversityDepartment of Pharmacology, Shenyang Medical CollegeDepartment of Neurosurgery, Shengjing Hospital of China Medical UniversityDepartment of Neurosurgery, Shengjing Hospital of China Medical UniversityDepartment of Neurosurgery, Shengjing Hospital of China Medical UniversityDepartment of Neurobiology, School of Life Sciences, China Medical UniversityDepartment of Neurobiology, School of Life Sciences, China Medical UniversityDepartment of Neurosurgery, Shengjing Hospital of China Medical UniversityDepartment of Neurosurgery, Shengjing Hospital of China Medical UniversityDepartment of Neurobiology, School of Life Sciences, China Medical UniversityAbstract Background RNA binding proteins (RBPs) have been reported to interact with RNAs to regulate gene expression. Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs, which involved in the angiogenesis of tumor. The purpose of this study is to elucidate the potential roles and molecular mechanisms of MOV10 and circ-DICER1 in regulating the angiogenesis of glioma-exposed endothelial cells (GECs). Methods The expressions of circ-DICER1, miR-103a-3p and miR-382-5p were detected by real-time PCR. The expressions of MOV10, ZIC4, Hsp90 and PI3K/Akt were detected by real-time PCR or western blot. The binding ability of circ-SHKBP1 and miR-544a / miR-379, ZIC4 and miR-544a / miR-379 were analyzed with Dual-Luciferase Reporter System or RIP experiment. The direct effects of ZIC4 on the Hsp90β promoter were analyzed by the ChIP experiment. The cell viability, migration and tube formation in vitro were detected by CCK-8, Transwell assay and Matrigel tube formation assay. The angiogenesis in vivo was evaluated by Matrigel plug assay. Student’s t-test (two tailed) was used for comparisons between two groups. One-way analysis of variance (ANOVA) was used for multi-group comparisons followed by Bonferroni post-hoc analysis. Results The expressions of RNA binding proteins MOV10, circ-DICER1, ZIC4, and Hsp90β were up-regulated in GECs, while miR103a-3p/miR-382-5p were down-regulated. MOV10 binding circ-DICER1 regulated the cell viability, migration, and tube formation of GECs. And the effects of both MOV10 and circ-DICER1 silencing were better than the effects of MOV10 or circ-DICER1 alone silencing. In addition, circ-DICER1 acts as a molecular sponge to adsorb miR-103a-3p / miR-382-5p and impair the negative regulation of miR-103a-3p / miR-382-5p on ZIC4 in GECs. Furthermore, ZIC4 up-regulates the expression of its downstream target Hsp90β, and Hsp90 promotes the cell viability, migration, and tube formation of GECs by activating PI3K/Akt signaling pathway. Conclusions MOV10 / circ-DICER1 / miR-103a-3p (miR-382-5p) / ZIC4 pathway plays a vital role in regulating the angiogenesis of glioma. Our findings not only provides novel mechanisms for the angiogenesis of glioma, but also provide potential targets for anti-angiogenesis therapies of glioma.http://link.springer.com/article/10.1186/s13046-018-0990-1MOV10Circ-DICER1miR-103a-3pmiR-382-5pGliomasAngiogenesis
spellingShingle Qianru He
Lini Zhao
Xiaobai Liu
Jian Zheng
Yunhui Liu
Libo Liu
Jun Ma
Heng Cai
Zhen Li
Yixue Xue
MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change
Journal of Experimental & Clinical Cancer Research
MOV10
Circ-DICER1
miR-103a-3p
miR-382-5p
Gliomas
Angiogenesis
title MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change
title_full MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change
title_fullStr MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change
title_full_unstemmed MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change
title_short MOV10 binding circ-DICER1 regulates the angiogenesis of glioma via miR-103a-3p/miR-382-5p mediated ZIC4 expression change
title_sort mov10 binding circ dicer1 regulates the angiogenesis of glioma via mir 103a 3p mir 382 5p mediated zic4 expression change
topic MOV10
Circ-DICER1
miR-103a-3p
miR-382-5p
Gliomas
Angiogenesis
url http://link.springer.com/article/10.1186/s13046-018-0990-1
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