Targeting the cuproptosis‑associated gene COL22A1 in glioblastoma using EMD‑1204831 and kaempferol.

Abstract

Glioblastoma (GBM) is a disease with high morbidity and poor prognosis. The combination of traditional Chinese and Western medicine and cuproptosis are known to serve important roles in the treatment of GBM. However, targeting cuproptosis to treat GBM by combining traditional Chinese and Western medicine has not been extensively investigated. Therefore, the present study focused on the diagnosis and treatment of GBM based on cuproptosis. Through a bioinformatics approach, a cuproptosis‑related prognostic model was first constructed. Next, this prognostic model was found to be closely related to immune infiltration, DNA mutation and DNA methylation through multi‑omics analysis. The present study indicated the cell clusters in GBM tissues and the risk scores in each cluster based on single‑cell sequencing data derived from Gene Expression Omnibus. Notably, by screening the CellMiner database, EMD‑1204831 was found to exhibit a high correlation with the risk score. Next, through network pharmacology and molecular docking analysis, the risk score‑related gene collagen type XXII α1 chain (COL22A1) was identified as the target of kaempferol, which is the active component of Ginseng. Notably, kaempferol could decrease the proliferation of GBM cells by inhibiting COL22A1 expression in cell experiments. Finally, kaempferol and EMD‑1204831 had an obvious inhibitory effect on the growth of GBM and sensitized GBM to cuproptosis inducers via COL22A1 in cell and animal experiments. Overall, the present study revealed a cuproptosis‑related combined regimen for GBM.