P53/miR-154 Pathway Regulates the Epithelial-Mesenchymal Transition in Glioblastoma Multiforme Cells by Targeting TCF12
Gang Zhu,1,* Shirong Yang,2,* Ronglin Wang,3,* Jie Lei,4 Peigang Ji,1 Jiancai Wang,1 Kai Tao,1 Chen Yang,1 Shunnan Ge,1 Liang Wang1 1Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Gen...
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| Autores principales: | , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/11d48ca267184097805b27b855f1087c |
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| Sumario: | Gang Zhu,1,* Shirong Yang,2,* Ronglin Wang,3,* Jie Lei,4 Peigang Ji,1 Jiancai Wang,1 Kai Tao,1 Chen Yang,1 Shunnan Ge,1 Liang Wang1 1Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 2Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Neurosurgery, Wuhan General Hospital of PLA, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang Wang; Shunnan GeDepartment of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xinsi Road, Xi’an, 710038, People’s Republic of ChinaTel +86-29-84717851; Tel +86-29-84717824Email drwangliang@126.com; gesn8561@163.comPurpose: Glioblastoma multiforme (GBM) is an aggressive brain tumor with a rather short survival time. Mutation of p53 has been observed and reported to play critical roles in the progression of GBM. However, the pathological mechanisms are still unclear. This study was designed to identify the role of miR-154 in mediating the biological functions of p53 in glioblastoma multiforme.Methods: In the current study, the expression of miR-154 in GBM tissue samples and cell lines with wt-p53 or mutant p53 was evaluated. The functions of miR-154 in tumor migration, invasion and epithelial-mesenchymal transition were analyzed in vitro. A luciferase reporter assay was used to identify the target of miR-154.Results: We found that expression of miR-154 was much lower in patient tissues with mutant p53. Further study revealed that p53 was a transcription factor of miR-154 and that the R273H mutation led to its inactivation. In addition, overexpression of miR-154 remarkably suppressed cell migration, invasion and EMT in vitro and tumor growth in vivo. Moreover, TCF12 was proven to be a direct target of miR-154, and the tumor suppressive effect of miR-154 was reversed by TCF12.Conclusion: Overall, miR-154, which was regulated by wt-p53, inhibited migration, invasion and EMT of GBM cells by targeting TCF12, indicating that miR-154 may act as a biomarker and that the p53/miR-154/TCF12 pathway could be a potential therapeutic target for GBM.Keywords: glioblastoma, p53, microRNA, EMT, TCF12 |
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