P53/miR-154 Pathway Regulates the Epithelial-Mesenchymal Transition in Glioblastoma Multiforme Cells by Targeting TCF12.
P53/miR-154 Pathway Regulates the Epithelial-Mesenchymal Transition in Glioblastoma Multiforme Cells by Targeting TCF12.
复制标题
P53/miR-154 通路通过靶向 TCF12 调节多形性胶质母细胞瘤细胞的上皮-间质转化。
DOI：
10.2147/ndt.s273578
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发表时间：
2021
影响因子：
3.2
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Zhu G;Yang S;Wang R;Lei J;Ji P;Wang J;Tao K;Yang C;Ge S;Wang L
多形性胶质母细胞瘤（GBM）是一种侵袭性脑肿瘤，生存时间相当短。p53突变已被观察到并报道在GBM的进展中起关键作用。然而，其病理机制尚不清楚。本研究旨在确定miR-154在多形性胶质母细胞瘤中介导p53生物学功能的作用。在本研究中，评估了miR-154在GBM组织样品和具有wt-p53或突变p53的细胞系中的表达。体外分析miR-154在肿瘤迁移、侵袭和上皮-间质转化中的作用。荧光素酶报告基因测定用于鉴定miR-154的靶标。我们发现miR-154的表达在具有突变型p53的患者组织中低得多。进一步的研究表明p53是miR-154的转录因子，R273 H突变导致其失活。此外，miR-154的过表达显著抑制体外细胞迁移、侵袭和EMT以及体内肿瘤生长。此外，TCF 12被证明是miR-154的直接靶点，并且miR-154的肿瘤抑制作用被TCF 12逆转。总体而言，受wt-p53调控的miR-154通过靶向TCF 12抑制GBM细胞的迁移、侵袭和EMT，表明miR-154可能作为生物标志物，并且p53/miR-154/TCF 12途径可能是GBM的潜在治疗靶点。
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.