P53/miR-154 Pathway Regulates the Epithelial-Mesenchymal Transition in Glioblastoma Multiforme Cells by Targeting TCF12.
EMT
TCF12
glioblastoma
microRNA
p53
Journal
Neuropsychiatric disease and treatment
ISSN: 1176-6328
Titre abrégé: Neuropsychiatr Dis Treat
Pays: New Zealand
ID NLM: 101240304
Informations de publication
Date de publication:
2021
2021
Historique:
received:
31
07
2020
accepted:
18
01
2021
entrez:
5
3
2021
pubmed:
6
3
2021
medline:
6
3
2021
Statut:
epublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 33664574
doi: 10.2147/NDT.S273578
pii: 273578
pmc: PMC7924251
doi:
Types de publication
Journal Article
Langues
eng
Pagination
681-693Informations de copyright
© 2021 Zhu et al.
Déclaration de conflit d'intérêts
All authors report no conflicts of interest in this work.
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