FRAT1 promotes the angiogenic properties of human glioblastoma cells via VEGFA

Yang,Biao; Liu,Dong; Ren,Ye-Qing; Sun,Yan-Qi; Zhang,Jian-Ping; Wang,Xiao-Gang; Wu,Yong-Qiang; Wang,Shu-Le; Guo,Shi-Hao; Guo,Geng

doi:10.3892/mmr.2022.12611

FRAT1 promotes the angiogenic properties of human glioblastoma cells via VEGFA

Authors:
- Biao Yang
- Dong Liu
- Ye-Qing Ren
- Yan-Qi Sun
- Jian-Ping Zhang
- Xiao-Gang Wang
- Yong-Qiang Wu
- Shu-Le Wang
- Shi-Hao Guo
- Geng Guo
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Affiliations: Department of Neurosurgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Neurosurgery, The Affiliated Liuzhou People's Hospital of Guangxi Medical University, Liuzhou, Guangxi Zhuang Autonomous Region 545006, P.R. China
Published online on: January 20, 2022 https://doi.org/10.3892/mmr.2022.12611
Article Number: 95

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Abstract

Glioblastoma is a common central nervous system tumor and despite considerable advancements in treatment patient prognosis remains poor. Angiogenesis is a significant prognostic factor in glioblastoma, anti‑angiogenic treatments represent a promising therapeutic approach. Vascular endothelial growth factor A (VEGFA) is a predominant regulator of angiogenesis and mounting evidence suggests that the Wnt signaling pathway serves a significant role in tumor angiogenesis. As a positive regulator of the Wnt/β‑catenin signaling pathway, frequently rearranged in advanced T‑cell lymphomas‑1 (FRAT1) is highly expressed in human glioblastoma and is significantly associated with glioblastoma growth, invasion and migration, as well as poor patient prognosis. Bioinformatics analysis demonstrated that both VEGFA and FRAT1 were highly expressed in most tumor tissues and associated with prognosis. However, whether and how FRAT1 is involved in angiogenesis remains to be elucidated. In the present study, the relationship between FRAT1 and VEGFA in angiogenesis was investigated using the human glioblastoma U251 cell line. Small interfering RNAs (siRNAs) were used to silence FRAT1 expression in U251 cells, and the mRNA and protein expression levels of VEGFA, as well as the concentration of VEGFA in U251 cell supernatants, were determined using reverse transcription‑quantitative PCR, western blotting and ELISA. A tube formation assay was conducted to assess angiogenesis. The results demonstrated that siRNA knockdown significantly decreased the protein expression levels of FRAT1 in U251 cells and markedly decreased the mRNA and protein expression levels of VEGFA. Furthermore, the concentration of VEGFA in the cell supernatant was significantly reduced and angiogenesis was suppressed. These results suggested that FRAT1 may promote VEGFA secretion and angiogenesis in human glioblastoma cells via the Wnt/β‑catenin signaling pathway, supporting the potential use of FRAT1 as a promising therapeutic target in human glioblastoma.

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