Research Paper Volume 13, Issue 17 pp 21587—21598
FOXN3 inhibits cell proliferation and invasion via modulating the AKT/MDM2/p53 axis in human glioma
- 1 Department of Neurosurgery, Taihe Affiliated Hospital of Hubei University of Medicine, Shiyan 442000, China
- 2 First School of Clinical Medicine, Hubei University of Medicine, Shiyan 442000, China
- 3 Department of Pediatrics, Taihe Affiliated Hospital of Hubei University of Medicine, Shiyan 442000, China
- 4 Department of Rehabilitation, Taihe Affiliated Hospital of Hubei University of Medicine, Shiyan 442000, China
Received: May 9, 2021 Accepted: July 30, 2021 Published: September 12, 2021https://doi.org/10.18632/aging.203499
How to Cite
Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.