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CUX1 Facilitates the Development of Oncogenic Properties Via Activating Wnt/β-Catenin Signaling Pathway in Glioma

Background: Homeobox cut like 1 (CUX1), which often presents aberrated expression in many cancer cells, exerts a crucial role in tumorigenesis. Evidence describing CUX1 in gliomagenesis is scarce, and the effects of CUX1 on the Wnt/β-catenin pathway have not been reported. Our study aimed to explore...

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Autores principales: Feng, Fan, Zhao, Zongqing, Zhou, Yunfei, Cheng, Yanhao, Wu, Xiujie, Heng, Xueyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377541/
https://www.ncbi.nlm.nih.gov/pubmed/34422906
http://dx.doi.org/10.3389/fmolb.2021.705008
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author Feng, Fan
Zhao, Zongqing
Zhou, Yunfei
Cheng, Yanhao
Wu, Xiujie
Heng, Xueyuan
author_facet Feng, Fan
Zhao, Zongqing
Zhou, Yunfei
Cheng, Yanhao
Wu, Xiujie
Heng, Xueyuan
author_sort Feng, Fan
collection PubMed
description Background: Homeobox cut like 1 (CUX1), which often presents aberrated expression in many cancer cells, exerts a crucial role in tumorigenesis. Evidence describing CUX1 in gliomagenesis is scarce, and the effects of CUX1 on the Wnt/β-catenin pathway have not been reported. Our study aimed to explore the biological functions and molecular mechanisms involved in CUX1 activity in glioma. Methods: Datasets for bioinformatics analysis were obtained from the GEO, TCGA, CGGA, GTEX and CCLE databases. qRT-PCR, western blotting (WB), and immunohistochemistry (IHC) assays were used to investigate the expression patterns of CUX1 among glioma and brain tissues. CUX1 knockdown and overexpression vectors were transfected into glioma cell lines, the CCK-8, clone formation assay, wound healing, Transwell assay, and flow cytometry were performed to detect changes in cell viability, invasiveness, and the cell cycle. WB and immunofluorescence (IF) assays were used to explore changes in cell cycle-related and Wnt/β-catenin signaling protein levels. Results: Overexpression of CUX1 was identified in glioma tissues, and especially in glioblastoma (GBM), when compared to normal controls and correlated with poor prognosis. In comparison with untreated cells, TJ905 glioma cells overexpressing CUX1 showed higher proliferation and invasion abilities and S phase cell-cycle arrest, while the knockdown of CUX1 suppressed cell invasive ability and induced G1 phase arrest. Active Wnt/β-catenin signaling was enriched and clustered in a CUX1-associated GSEA/GSVA analysis. IF and WB assays indicated that CUX1 regulated the distribution of Axin2/β-catenin in glioma cells and regulated the expression of proteins downstream of the Wnt/β-catenin signaling pathway, suggesting that CUX1 served as an upstream positive regulator of the Wnt/β-catenin pathway. Finally, the knockdown of Axin2 or β-catenin could reverse the tumor-promoting effects caused by CUX1 overexpression, suggesting that CUX1 induced gliomagenesis and malignant phenotype by activating the Wnt/β-catenin signaling pathway. Conclusion: Our data suggested that the transcription factor CUX1 could be a novel therapeutic target for glioma with gene therapy.
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spelling pubmed-83775412021-08-21 CUX1 Facilitates the Development of Oncogenic Properties Via Activating Wnt/β-Catenin Signaling Pathway in Glioma Feng, Fan Zhao, Zongqing Zhou, Yunfei Cheng, Yanhao Wu, Xiujie Heng, Xueyuan Front Mol Biosci Molecular Biosciences Background: Homeobox cut like 1 (CUX1), which often presents aberrated expression in many cancer cells, exerts a crucial role in tumorigenesis. Evidence describing CUX1 in gliomagenesis is scarce, and the effects of CUX1 on the Wnt/β-catenin pathway have not been reported. Our study aimed to explore the biological functions and molecular mechanisms involved in CUX1 activity in glioma. Methods: Datasets for bioinformatics analysis were obtained from the GEO, TCGA, CGGA, GTEX and CCLE databases. qRT-PCR, western blotting (WB), and immunohistochemistry (IHC) assays were used to investigate the expression patterns of CUX1 among glioma and brain tissues. CUX1 knockdown and overexpression vectors were transfected into glioma cell lines, the CCK-8, clone formation assay, wound healing, Transwell assay, and flow cytometry were performed to detect changes in cell viability, invasiveness, and the cell cycle. WB and immunofluorescence (IF) assays were used to explore changes in cell cycle-related and Wnt/β-catenin signaling protein levels. Results: Overexpression of CUX1 was identified in glioma tissues, and especially in glioblastoma (GBM), when compared to normal controls and correlated with poor prognosis. In comparison with untreated cells, TJ905 glioma cells overexpressing CUX1 showed higher proliferation and invasion abilities and S phase cell-cycle arrest, while the knockdown of CUX1 suppressed cell invasive ability and induced G1 phase arrest. Active Wnt/β-catenin signaling was enriched and clustered in a CUX1-associated GSEA/GSVA analysis. IF and WB assays indicated that CUX1 regulated the distribution of Axin2/β-catenin in glioma cells and regulated the expression of proteins downstream of the Wnt/β-catenin signaling pathway, suggesting that CUX1 served as an upstream positive regulator of the Wnt/β-catenin pathway. Finally, the knockdown of Axin2 or β-catenin could reverse the tumor-promoting effects caused by CUX1 overexpression, suggesting that CUX1 induced gliomagenesis and malignant phenotype by activating the Wnt/β-catenin signaling pathway. Conclusion: Our data suggested that the transcription factor CUX1 could be a novel therapeutic target for glioma with gene therapy. Frontiers Media S.A. 2021-08-06 /pmc/articles/PMC8377541/ /pubmed/34422906 http://dx.doi.org/10.3389/fmolb.2021.705008 Text en Copyright © 2021 Feng, Zhao, Zhou, Cheng, Wu and Heng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Feng, Fan
Zhao, Zongqing
Zhou, Yunfei
Cheng, Yanhao
Wu, Xiujie
Heng, Xueyuan
CUX1 Facilitates the Development of Oncogenic Properties Via Activating Wnt/β-Catenin Signaling Pathway in Glioma
title CUX1 Facilitates the Development of Oncogenic Properties Via Activating Wnt/β-Catenin Signaling Pathway in Glioma
title_full CUX1 Facilitates the Development of Oncogenic Properties Via Activating Wnt/β-Catenin Signaling Pathway in Glioma
title_fullStr CUX1 Facilitates the Development of Oncogenic Properties Via Activating Wnt/β-Catenin Signaling Pathway in Glioma
title_full_unstemmed CUX1 Facilitates the Development of Oncogenic Properties Via Activating Wnt/β-Catenin Signaling Pathway in Glioma
title_short CUX1 Facilitates the Development of Oncogenic Properties Via Activating Wnt/β-Catenin Signaling Pathway in Glioma
title_sort cux1 facilitates the development of oncogenic properties via activating wnt/β-catenin signaling pathway in glioma
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377541/
https://www.ncbi.nlm.nih.gov/pubmed/34422906
http://dx.doi.org/10.3389/fmolb.2021.705008
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