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Updated: Oct 20, 2025

Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
FOXN3 inhibits cell proliferation and invasion via modulating the AKT/MDM2/p53 axis in human glioma
Chaojia Wang1, Hanjun Tu2, Ling Yang3
1Department of Neurosurgery, Taihe Affiliated Hospital of Hubei University of Medicine, Shiyan 442000, China.
Abstract:
This study aimed to evaluate the biological role of forkhead box N3 (FOXN3) in human glioma and clarify the possible molecular mechanisms. FOXN3 expression patterns in clinical tissue specimens were characterized via qPCR and Western blotting. Kaplan-Meier survival curve was applied to assess the correlation between FOXN3 expression and overall survival. Effects of FOXN3 over-expression and depletion on glioma cell proliferation, apoptosis, migration and invasion were assessed by CCK8, colony formation assay, flow cytometry, scratch wound healing assay and Transwell invasion assay, respectively. Moreover, the involvement of AKT/murine double minute 2 (MDM2)/p53 pathway was evaluated. Additionally, tumor transplantation model assay was performed to determine the effects of FOXN3 over-expression on glioma cell growth in vivo. Results showed that FOXN3 was significantly down-regulated in glioma tissues compared with normal tissues. Patients with lower FOXN3 expression exhibited a shorter overall survival time. Gain- and loss-of-function analyses demonstrated that FOXN3 over-expression significantly suppressed proliferation, survival and motility of glioma cells, whereas FOXN3 knockdown remarkably promoted glioma cell proliferation, survival and motility. Furthermore, FOXN3 over-expression inhibited the activation of AKT/MDM2/p53 signaling pathway in glioma cells, while FOXN3 depletion facilitated its activation. Additionally, tumor xenograft assays revealed that FOXN3 over-expression retarded glioma cell growth in vivo. Collectively, these findings indicate that FOXN3 inhibits cell growth and invasion through inactivating the AKT/MDM2/p53 signaling pathway and that FOXN3-AKT/MDM2/p53 axis may represent a novel therapeutic target for glioma patients.
Insights
Forkhead box N3 (FOXN3) is downregulated in glioma, suppressing tumor growth and invasion. Restoring FOXN3 inhibits proliferation and motility by inactivating the AKT/MDM2/p53 pathway, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioma is a primary brain tumor with limited therapeutic options.
- The role of forkhead box N3 (FOXN3) in glioma pathogenesis is not well understood.
Purpose of the Study:
- To investigate the biological role of FOXN3 in human glioma.
- To elucidate the molecular mechanisms underlying FOXN3's function in glioma.
Main Methods:
- Quantitative PCR and Western blotting for FOXN3 expression analysis.
- Cell proliferation, apoptosis, migration, and invasion assays (CCK8, colony formation, flow cytometry, scratch wound, Transwell).
- In vivo tumor xenograft models and analysis of the AKT/MDM2/p53 signaling pathway.
Main Results:
- FOXN3 expression is significantly downregulated in glioma tissues.
- Lower FOXN3 levels correlate with shorter patient survival.
- FOXN3 overexpression suppresses glioma cell proliferation, survival, and motility, while FOXN3 knockdown promotes these.
- FOXN3 inactivates the AKT/MDM2/p53 signaling pathway, inhibiting tumor growth in vitro and in vivo.
Conclusions:
- FOXN3 acts as a tumor suppressor in glioma.
- The FOXN3-AKT/MDM2/p53 axis represents a potential therapeutic target for glioma treatment.
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