FOXN3 inhibits cell proliferation and invasion via modulating the AKT/MDM2/p53 axis in human glioma.

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.

• Authors: Chaojia Wang, Hanjun Tu, Ling Yang, Chunming Ma, Juntao Hu, Jie Luo, Hui Wang
• Journal: Aging (Aging (Albany NY)) Vol. 13 Issue 17 Pg. 21587-21598 (09 12 2021) ISSN: 1945-4589 [Electronic] United States
• PMID: 34511432 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Cycle Proteins
• FOXN3 protein, human
• Forkhead Transcription Factors
• Tumor Suppressor Protein p53
• Proto-Oncogene Proteins c-mdm2
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Apoptosis (physiology)
• Cell Cycle Proteins (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Forkhead Transcription Factors (genetics, metabolism)
• Glioma (metabolism, pathology)
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Proto-Oncogene Proteins c-akt (metabolism)
• Proto-Oncogene Proteins c-mdm2 (metabolism)
• Signal Transduction
• Tumor Suppressor Protein p53 (metabolism)
• Xenograft Model Antitumor Assays