Upregulated FKBP1A Suppresses Glioblastoma Cell Growth via Apoptosis Pathway
Shaoyi Cai1, Zhiyou Chen1, Heng Tang1
1Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.
Abstract:
Glioblastoma (GBM), the most deadly primary brain tumor, presents a major medical difficulty. The need for better therapeutic targets in GBM is therefore urgent. A growing body of evidence suggests that the gene FKBP1A plays an important role in tumor progression and may be therapeutically useful. However, the role of FKBP1A in glioblastoma and the underlying biologic mechanism remain unclear. The purpose of this study was to identify the role of FKBP1A in GBM and its molecular mechanism. We demonstrated that FKBP1A was the hub gene in GBM via a weighted correlation network analysis (WGCNA) and differentially expressed genes (DEGs) analysis based on the bulk RNA-seq data from TCGA and GTEx. Afterwards, we proved that the upregulated FKBP1A protein could promote GBM cell death by CCK-8 assays in U87MG and t98g GBM cell lines. We further demonstrated two key pathways of FKBP1A in GBM by bioinformatics methods: 'Apoptosis' and 'mTOR signaling pathway'. Subsequently, the key pathways were verified by flow cytometry and Western blot. We identified that upregulated FKBP1A could inhibit GBM growth via the apoptosis pathway. Together, these findings may contribute to future GBM treatment.
Insights
FKBP1A is a key gene in glioblastoma (GBM) that promotes cancer cell death. Upregulated FKBP1A inhibits GBM growth by activating the apoptosis pathway, offering potential new therapeutic strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioblastoma (GBM) is a lethal brain tumor with urgent need for novel therapeutic targets.
- The gene FKBP1A is implicated in tumor progression, but its specific role and mechanism in GBM remain unclear.
Purpose of the Study:
- To elucidate the role of FKBP1A in glioblastoma.
- To identify the molecular mechanisms underlying FKBP1A's function in GBM.
Main Methods:
- Weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis using TCGA and GTEx data.
- Cell viability assays (CCK-8) on U87MG and t98g GBM cell lines.
- Bioinformatic analysis to identify key signaling pathways, followed by flow cytometry and Western blot validation.
Main Results:
- FKBP1A was identified as a hub gene in glioblastoma.
- Upregulated FKBP1A protein expression was shown to induce GBM cell death.
- The apoptosis and mTOR signaling pathways were identified as key mediators of FKBP1A's function.
- Validation confirmed that increased FKBP1A inhibits GBM growth through the apoptosis pathway.
Conclusions:
- FKBP1A plays a significant role in glioblastoma progression and cell death.
- Targeting FKBP1A, particularly through the apoptosis pathway, represents a promising therapeutic strategy for glioblastoma.
- These findings provide a foundation for developing novel treatments for this aggressive brain cancer.
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