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Aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the progression of gliomas
Gliomas are the most common form of malignant tumour in the central nervous system. However, the molecular mechanism of the tumorigenesis and progression of gliomas remains unclear. In this study, we used the GEO database to identify genes differentially expressed in gliomas and predict the prognosi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520292/ https://www.ncbi.nlm.nih.gov/pubmed/32667745 http://dx.doi.org/10.1111/jcmm.15435 |
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author | Zeng, Wen‐Jing Cheng, Quan Wen, Zhi‐Peng Wang, Jie‐Ya Chen, Yan‐Hong Zhao, Jie Gong, Zhi‐Cheng Chen, Xiao‐Ping |
author_facet | Zeng, Wen‐Jing Cheng, Quan Wen, Zhi‐Peng Wang, Jie‐Ya Chen, Yan‐Hong Zhao, Jie Gong, Zhi‐Cheng Chen, Xiao‐Ping |
author_sort | Zeng, Wen‐Jing |
collection | PubMed |
description | Gliomas are the most common form of malignant tumour in the central nervous system. However, the molecular mechanism of the tumorigenesis and progression of gliomas remains unclear. In this study, we used the GEO database to identify genes differentially expressed in gliomas and predict the prognosis of glioma. We observed that ASPM mRNA was increased obviously in glioma tissue, and higher ASPM mRNA expression predicted worse disease prognosis. ASPM was highly expressed in glioma cell lines U87‐MG and U251, and knockdown of ASPM expression in these cells significantly repressed the proliferation, migration and invasion ability and induced G0/G1 phase arrest. In addition, down‐regulation of ASPM suppressed the growth of glioma in nude mice. Five potential binding sites for transcription factor FoxM1 were predicted in the ASPM promoter. FoxM1 overexpression significantly increased the expression of ASPM and promoted the proliferation and migration of glioma cells, which was abolished by ASPM ablation. ChIP and dual‐luciferase reporter analysis confirmed that FoxM1 bound to the ASPM promoter at −236 to ‐230 bp and −1354 to ‐1348 bp and activated the transcription of ASPM directly. Collectively, our results demonstrated for the first time that aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the malignant properties of glioma cells. |
format | Online Article Text |
id | pubmed-7520292 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75202922020-09-30 Aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the progression of gliomas Zeng, Wen‐Jing Cheng, Quan Wen, Zhi‐Peng Wang, Jie‐Ya Chen, Yan‐Hong Zhao, Jie Gong, Zhi‐Cheng Chen, Xiao‐Ping J Cell Mol Med Original Articles Gliomas are the most common form of malignant tumour in the central nervous system. However, the molecular mechanism of the tumorigenesis and progression of gliomas remains unclear. In this study, we used the GEO database to identify genes differentially expressed in gliomas and predict the prognosis of glioma. We observed that ASPM mRNA was increased obviously in glioma tissue, and higher ASPM mRNA expression predicted worse disease prognosis. ASPM was highly expressed in glioma cell lines U87‐MG and U251, and knockdown of ASPM expression in these cells significantly repressed the proliferation, migration and invasion ability and induced G0/G1 phase arrest. In addition, down‐regulation of ASPM suppressed the growth of glioma in nude mice. Five potential binding sites for transcription factor FoxM1 were predicted in the ASPM promoter. FoxM1 overexpression significantly increased the expression of ASPM and promoted the proliferation and migration of glioma cells, which was abolished by ASPM ablation. ChIP and dual‐luciferase reporter analysis confirmed that FoxM1 bound to the ASPM promoter at −236 to ‐230 bp and −1354 to ‐1348 bp and activated the transcription of ASPM directly. Collectively, our results demonstrated for the first time that aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the malignant properties of glioma cells. John Wiley and Sons Inc. 2020-07-15 2020-09 /pmc/articles/PMC7520292/ /pubmed/32667745 http://dx.doi.org/10.1111/jcmm.15435 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Zeng, Wen‐Jing Cheng, Quan Wen, Zhi‐Peng Wang, Jie‐Ya Chen, Yan‐Hong Zhao, Jie Gong, Zhi‐Cheng Chen, Xiao‐Ping Aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the progression of gliomas |
title | Aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the progression of gliomas |
title_full | Aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the progression of gliomas |
title_fullStr | Aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the progression of gliomas |
title_full_unstemmed | Aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the progression of gliomas |
title_short | Aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the progression of gliomas |
title_sort | aberrant aspm expression mediated by transcriptional regulation of foxm1 promotes the progression of gliomas |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520292/ https://www.ncbi.nlm.nih.gov/pubmed/32667745 http://dx.doi.org/10.1111/jcmm.15435 |
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