Research Paper Volume 12, Issue 11 pp 10594—10613
Coagulation factor 2 thrombin receptor promotes malignancy in glioma under SOX2 regulation
- 1 Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, PR. China
- 2 Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, PR. China
- 3 Department of Operating Theatre, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, PR. China
Received: December 17, 2019 Accepted: April 17, 2020 Published: June 7, 2020
https://doi.org/10.18632/aging.103281How to Cite
Copyright © 2020 Gao 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.
Abstract
Glioma is the most common human primary brain cancer with high mortality and unfavorable clinical outcome. Coagulation factor 2 thrombin receptor (F2R), is a key component in the thrombosis process and has been demonstrated upregulated in various cancers. However, the effect and molecular mechanisms of F2R in glioma remains unclear. In our study, we confirmed that the expression of F2R was upregulated in glioma and predicted poor prognosis. Gene Set Enrichment Analysis (GSEA) and function assays demonstrated that F2R overexpression promoted glioma cell proliferation, metastasis and epithelial-mesenchymal transition (EMT) in vitro and tumor growth in vivo. Then, we identified and validated F2R was the target gene of SRY-box 2 (SOX2) by dual luciferase reporter assay and chromatin immunoprecipitation assay. Besides, High expression of F2R in malignant glioma was associated with β-catenint signaling pathway activation. Our findings conclude that F2R promotes glioma cell proliferation and metastasis under SOX2 and actives WNT/β-catenin Signaling pathway, which provides novel insight to the therapeutic regimen in glioma.
Abbreviations
F2R: Coagulation factor 2 thrombin receptor; SOX2: SRY-box 2; GSEA: Gene Set Enrichment Analysis; GBM: Glioblastoma multiforme; TCGA: The Cancer Genome Atlas; Sh-RNA: Short hairpin RNA; ChIP: Chromatin immunoprecipitation; EMT: epithelial-mesenchymal transition; GBM: Glioblastoma multiforme; LGG: Brain Lower Grade Glioma.