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Akt/FoxM1 signaling pathway-mediated upregulation of MYBL2 promotes progression of human glioma
BACKGROUND: MYB-related protein B (B-MYB/MYBL2), a member of the myeloblastosis family of transcription factors, has been reported for its role in the genesis and progression of tumors. Forkhead box M1 (FoxM1), another transcriptional factor, is considered to be an independent predictor of poor surv...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547476/ https://www.ncbi.nlm.nih.gov/pubmed/28784180 http://dx.doi.org/10.1186/s13046-017-0573-6 |
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author | Zhang, Xue LV, Qiao-Li Huang, Yuan-Tao Zhang, Li-Hua Zhou, Hong-Hao |
author_facet | Zhang, Xue LV, Qiao-Li Huang, Yuan-Tao Zhang, Li-Hua Zhou, Hong-Hao |
author_sort | Zhang, Xue |
collection | PubMed |
description | BACKGROUND: MYB-related protein B (B-MYB/MYBL2), a member of the myeloblastosis family of transcription factors, has been reported for its role in the genesis and progression of tumors. Forkhead box M1 (FoxM1), another transcriptional factor, is considered to be an independent predictor of poor survival in many solid cancers. The aim of the present study was to investigate the clinical significance of the correlation between MYBL2 and FoxM1 in glioma and the possible mechanism of FoxM1and MYBL2 expression. METHODS: MYBL2 and FoxM1expression in cancerous tissues and cell lines were determined by reverse transcription-PCR (RT-PCR), Western blotting and immunostaining. The co-expression of MYBL2 and FoxM1 was analyzed in low-grade glioma (LGG) and glioblastoma (HGG) cohorts of TCGA using cBioportal and UCSC Xena. And, the role of MYBL2 and FoxM1 in glioma cell progression and the underlying mechanisms were studied by using small interfering RNA (si-RNA) and pcDNA3.1 + HAvectors. Furthermore, the effects of MYBL2 and FoxM1 in cell proliferation, cell cycle progression, apoptosis, migration, invasion, and adhesion were determined by cell proliferation assays, flow cytometry analysis, transwell migration and cell adhesion assay. RESULTS: MYBL2 and FoxM1 expression are significantly associated with clinical stages and overall survival of glioma patients. In cohorts of TCGA, patients with high MYBL2 but without radio-chemotherapy had the highest hazard ratio (adjusted HR = 5.29, 95% CI = 1.475–18.969, P < 0.05). Meanwhile, MYBL2 closely related to the FoxM1 expression in 79 glioma tissues (r = 0.742, p < 0.05) and LGG (r = 0.83) and HGG (r = 0.74) cohorts of TCGA. Down regulation of FoxM1 and MYBL2 by siRNAs induced the cell cycle arrest, apoptosis and EMT of glioma cells. Furthermore, inactivations of Akt/FoxM1 signaling by Akt inhibitor and siRNA-FoxM1 reduce the expression of MYBL2 in glioma cells. CONCLUSIONS: MYBL2 is a key downstream factor of Akt/FoxM1 signaling to promote progression of human glioma, and could be a new candidate gene for molecular targeting therapy and biomarker for radiotherapy of glioma. TRIAL REGISTRATION: CTXY-1300041-3-2. ChiCTR-COC-15006186. Registered date: 13 September 2013. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-017-0573-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5547476 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-55474762017-08-09 Akt/FoxM1 signaling pathway-mediated upregulation of MYBL2 promotes progression of human glioma Zhang, Xue LV, Qiao-Li Huang, Yuan-Tao Zhang, Li-Hua Zhou, Hong-Hao J Exp Clin Cancer Res Research BACKGROUND: MYB-related protein B (B-MYB/MYBL2), a member of the myeloblastosis family of transcription factors, has been reported for its role in the genesis and progression of tumors. Forkhead box M1 (FoxM1), another transcriptional factor, is considered to be an independent predictor of poor survival in many solid cancers. The aim of the present study was to investigate the clinical significance of the correlation between MYBL2 and FoxM1 in glioma and the possible mechanism of FoxM1and MYBL2 expression. METHODS: MYBL2 and FoxM1expression in cancerous tissues and cell lines were determined by reverse transcription-PCR (RT-PCR), Western blotting and immunostaining. The co-expression of MYBL2 and FoxM1 was analyzed in low-grade glioma (LGG) and glioblastoma (HGG) cohorts of TCGA using cBioportal and UCSC Xena. And, the role of MYBL2 and FoxM1 in glioma cell progression and the underlying mechanisms were studied by using small interfering RNA (si-RNA) and pcDNA3.1 + HAvectors. Furthermore, the effects of MYBL2 and FoxM1 in cell proliferation, cell cycle progression, apoptosis, migration, invasion, and adhesion were determined by cell proliferation assays, flow cytometry analysis, transwell migration and cell adhesion assay. RESULTS: MYBL2 and FoxM1 expression are significantly associated with clinical stages and overall survival of glioma patients. In cohorts of TCGA, patients with high MYBL2 but without radio-chemotherapy had the highest hazard ratio (adjusted HR = 5.29, 95% CI = 1.475–18.969, P < 0.05). Meanwhile, MYBL2 closely related to the FoxM1 expression in 79 glioma tissues (r = 0.742, p < 0.05) and LGG (r = 0.83) and HGG (r = 0.74) cohorts of TCGA. Down regulation of FoxM1 and MYBL2 by siRNAs induced the cell cycle arrest, apoptosis and EMT of glioma cells. Furthermore, inactivations of Akt/FoxM1 signaling by Akt inhibitor and siRNA-FoxM1 reduce the expression of MYBL2 in glioma cells. CONCLUSIONS: MYBL2 is a key downstream factor of Akt/FoxM1 signaling to promote progression of human glioma, and could be a new candidate gene for molecular targeting therapy and biomarker for radiotherapy of glioma. TRIAL REGISTRATION: CTXY-1300041-3-2. ChiCTR-COC-15006186. Registered date: 13 September 2013. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13046-017-0573-6) contains supplementary material, which is available to authorized users. BioMed Central 2017-08-07 /pmc/articles/PMC5547476/ /pubmed/28784180 http://dx.doi.org/10.1186/s13046-017-0573-6 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Zhang, Xue LV, Qiao-Li Huang, Yuan-Tao Zhang, Li-Hua Zhou, Hong-Hao Akt/FoxM1 signaling pathway-mediated upregulation of MYBL2 promotes progression of human glioma |
title | Akt/FoxM1 signaling pathway-mediated upregulation of MYBL2 promotes progression of human glioma |
title_full | Akt/FoxM1 signaling pathway-mediated upregulation of MYBL2 promotes progression of human glioma |
title_fullStr | Akt/FoxM1 signaling pathway-mediated upregulation of MYBL2 promotes progression of human glioma |
title_full_unstemmed | Akt/FoxM1 signaling pathway-mediated upregulation of MYBL2 promotes progression of human glioma |
title_short | Akt/FoxM1 signaling pathway-mediated upregulation of MYBL2 promotes progression of human glioma |
title_sort | akt/foxm1 signaling pathway-mediated upregulation of mybl2 promotes progression of human glioma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5547476/ https://www.ncbi.nlm.nih.gov/pubmed/28784180 http://dx.doi.org/10.1186/s13046-017-0573-6 |
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