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MDM2 induces EMT via the B-Raf signaling pathway through 14-3-3

MDM2 proto-oncogene, E3 ubiquitin protein ligase (MDM2) is a well-known oncogene and has been reported to be closely associated with epithelial-to-mesenchymal transition (EMT). The present study first demonstrated that the expression levels of MDM2 were markedly increased in TGF-β-induced EMT using...

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Autores principales: Ou, Mengting, Xu, Xichao, Chen, Ying, Li, Li, Zhang, Lu, Liao, Yi, Sun, Weichao, Quach, Christine, Feng, Jianguo, Tang, Liling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129971/
https://www.ncbi.nlm.nih.gov/pubmed/33955525
http://dx.doi.org/10.3892/or.2021.8071
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author Ou, Mengting
Xu, Xichao
Chen, Ying
Li, Li
Zhang, Lu
Liao, Yi
Sun, Weichao
Quach, Christine
Feng, Jianguo
Tang, Liling
author_facet Ou, Mengting
Xu, Xichao
Chen, Ying
Li, Li
Zhang, Lu
Liao, Yi
Sun, Weichao
Quach, Christine
Feng, Jianguo
Tang, Liling
author_sort Ou, Mengting
collection PubMed
description MDM2 proto-oncogene, E3 ubiquitin protein ligase (MDM2) is a well-known oncogene and has been reported to be closely associated with epithelial-to-mesenchymal transition (EMT). The present study first demonstrated that the expression levels of MDM2 were markedly increased in TGF-β-induced EMT using quantitative PCR and western blotting. In addition, MDM2 was demonstrated to be associated with pathological grade in clinical glioma samples by immunohistochemical staining. Furthermore, overexpression of MDM2 promoted EMT in glioma, lung cancer and breast cancer cell lines using a scratch wound migration assay. Subsequently, the present study explored the mechanism by which MDM2 promoted EMT and revealed that MDM2 induced EMT by upregulating EMT-related transcription factors via activation of the B-Raf signaling pathway through tyrosine 3-monooxygenase activation protein ε using RNA sequencing and western blotting. This mechanism depended on the p53 gene. Furthermore, in vivo experiments and the colony formation experiment demonstrated that MDM2 could promote tumor progression and induce EMT via the B-Raf signaling pathway. Since EMT contributes to increased drug resistance in tumor cells, the present study also explored the relationship between MDM2 and drug sensitivity using an MTT assay, and identified that MDM2 promoted cell insensitivity to silibinin treatment in an EMT-dependent manner. This finding is crucial for the development of cancer therapies and can also provide novel research avenues for future biological and clinical studies.
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spelling pubmed-81299712021-05-19 MDM2 induces EMT via the B-Raf signaling pathway through 14-3-3 Ou, Mengting Xu, Xichao Chen, Ying Li, Li Zhang, Lu Liao, Yi Sun, Weichao Quach, Christine Feng, Jianguo Tang, Liling Oncol Rep Articles MDM2 proto-oncogene, E3 ubiquitin protein ligase (MDM2) is a well-known oncogene and has been reported to be closely associated with epithelial-to-mesenchymal transition (EMT). The present study first demonstrated that the expression levels of MDM2 were markedly increased in TGF-β-induced EMT using quantitative PCR and western blotting. In addition, MDM2 was demonstrated to be associated with pathological grade in clinical glioma samples by immunohistochemical staining. Furthermore, overexpression of MDM2 promoted EMT in glioma, lung cancer and breast cancer cell lines using a scratch wound migration assay. Subsequently, the present study explored the mechanism by which MDM2 promoted EMT and revealed that MDM2 induced EMT by upregulating EMT-related transcription factors via activation of the B-Raf signaling pathway through tyrosine 3-monooxygenase activation protein ε using RNA sequencing and western blotting. This mechanism depended on the p53 gene. Furthermore, in vivo experiments and the colony formation experiment demonstrated that MDM2 could promote tumor progression and induce EMT via the B-Raf signaling pathway. Since EMT contributes to increased drug resistance in tumor cells, the present study also explored the relationship between MDM2 and drug sensitivity using an MTT assay, and identified that MDM2 promoted cell insensitivity to silibinin treatment in an EMT-dependent manner. This finding is crucial for the development of cancer therapies and can also provide novel research avenues for future biological and clinical studies. D.A. Spandidos 2021-07 2021-05-05 /pmc/articles/PMC8129971/ /pubmed/33955525 http://dx.doi.org/10.3892/or.2021.8071 Text en Copyright: © Ou et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Ou, Mengting
Xu, Xichao
Chen, Ying
Li, Li
Zhang, Lu
Liao, Yi
Sun, Weichao
Quach, Christine
Feng, Jianguo
Tang, Liling
MDM2 induces EMT via the B-Raf signaling pathway through 14-3-3
title MDM2 induces EMT via the B-Raf signaling pathway through 14-3-3
title_full MDM2 induces EMT via the B-Raf signaling pathway through 14-3-3
title_fullStr MDM2 induces EMT via the B-Raf signaling pathway through 14-3-3
title_full_unstemmed MDM2 induces EMT via the B-Raf signaling pathway through 14-3-3
title_short MDM2 induces EMT via the B-Raf signaling pathway through 14-3-3
title_sort mdm2 induces emt via the b-raf signaling pathway through 14-3-3
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129971/
https://www.ncbi.nlm.nih.gov/pubmed/33955525
http://dx.doi.org/10.3892/or.2021.8071
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