MDM2 induces EMT via the B-Raf signaling pathway through 14-3-3
MDM2 induces EMT via the B-Raf signaling pathway through 14-3-3
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MDM2 通过 B-Raf 信号通路通过 14-3-3 诱导 EMT
DOI：
10.3892/or.2021.8071
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发表时间：
2021-05
期刊：
影响因子：
4.2
通讯作者：
Tang Liling
中科院分区：
文献类型：
--
作者：
Ou Mengting;Xu Xichao;Chen Ying;Li Li;Zhang Lu;Liao Yi;Sun Weichao;Quach Christine;Feng Jianguo;Tang Liling
MDM 2原癌基因E3泛素蛋白连接酶（MDM 2）是一种已知的癌基因，与上皮细胞向间质细胞转化（EMT）密切相关。本研究首次通过定量PCR和Western blotting证实了TGF-β诱导的EMT中MDM 2的表达水平显著升高。此外，通过免疫组化染色证实MDM 2与临床胶质瘤样品中的病理分级相关。此外，使用划痕伤口迁移测定，MDM 2的过表达促进神经胶质瘤、肺癌和乳腺癌细胞系中的EMT。随后，本研究探讨了MDM 2促进EMT的机制，并通过RNA测序和蛋白质印迹法揭示MDM 2通过酪氨酸3-单加氧酶激活蛋白ε激活B-Raf信号通路上调EMT相关转录因子诱导EMT。这种机制依赖于p53基因。体内实验和殖民地形成实验证实MDM 2可通过B-Raf信号通路促进肿瘤进展并诱导EMT。由于EMT有助于增加肿瘤细胞的耐药性，因此本研究还使用MTT法探索了MDM 2与药物敏感性之间的关系，并确定MDM 2以EMT依赖的方式促进细胞对水飞蓟宾治疗的不敏感性。这一发现对于癌症治疗的发展至关重要，也可以为未来的生物学和临床研究提供新的研究途径。
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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影响因子：
4.4
作者：
Dimuthu R. Desilva;Elizabeth A. Jones;M. Favata;Bruce D. Jaffee;R. Magolda;J. Trzăskos;Peggy Scherle
通讯作者：
Dimuthu R. Desilva;Elizabeth A. Jones;M. Favata;Bruce D. Jaffee;R. Magolda;J. Trzăskos;Peggy Scherle
影响因子：
3.1
作者：
Zhang J;Zhou Y
通讯作者：
Zhou Y
影响因子：
8.8
作者：
Yang, Q.;Huang, J.;Wu, Q.;Cai, Y.;Zhu, L.;Lu, X.;Chen, S.;Chen, C.;Wang, Z.
通讯作者：
Wang, Z.
DOI：
--
发表时间：
2007-08
期刊：
The Journal of rheumatology
影响因子：
--
作者：
R. Kilani;W. Maksymowych;A. Aitken;G. Boire;Y. St-Pierre;Yunyuan Li;A. Ghahary
通讯作者：
R. Kilani;W. Maksymowych;A. Aitken;G. Boire;Y. St-Pierre;Yunyuan Li;A. Ghahary
影响因子：
44.1
作者：
Jihan K Osborne;Elma Zaganjor;M. Cobb
通讯作者：
Jihan K Osborne;Elma Zaganjor;M. Cobb