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Exploring the anti-gastric cancer mechanisms of Diosgenin through integrated network analysis, bioinformatics,
Zhangjun Yun1,2, Qianru Yang1,2, Chengyuan Xue1,2
1Department of Oncology and Hematology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
Background:
To comprehensively investigate the mechanism of action of Diosgenin elements against gastric cancer (GC).
Methods:
Targets of Diosgenin were collected from six databases, and enrichment analysis was used to identify its associated diseases and biological pathways. GC-related genes were identified using weighted gene co-expression network analysis. A multi-approach strategy, including network analysis, bioinformatics, single-cell RNA sequencing, Mendelian randomization, and cell experiments, was used to explore the anti-GC mechanisms of Diosgenin.
Results:
In this study, 605 Diosgenin targets were identified, with key involvement in cell apoptosis, TNF signaling, and platinum resistance pathways, demonstrating significant enrichment in GC. Diosgenin may exert its anti-GC effects through 311 targets, involving regulation of the cell cycle, p53, and FoxO signaling pathway. Key effectors, including CDK1, CCNA2, TOP2A, CHEK1, and PLK1, were identified. Single-cell sequencing indicated that TOP2A, HSP90AA1, and HSP90AB1 might be crucial immune regulatory targets of Diosgenin. Diosgenin significantly inhibited GC cell proliferation, colony formation, migration, and invasion. Evidence from western blot analysis indicates that Diosgenin exerts anti-GC effects by suppressing the expression of PLK1 and MDM2 proteins while upregulating p53 protein levels.
Conclusion:
These findings highlight Diosgenin's potential as a promising therapeutic agent for GC, offering a foundation for future research and clinical applications.
Insights
Diosgenin shows potential against gastric cancer (GC) by regulating cell cycle and apoptosis pathways. This natural compound inhibits GC cell growth and invasion, offering a promising therapeutic avenue.
Area of Science:
- Oncology
- Pharmacology
- Bioinformatics
Background:
- Gastric cancer (GC) remains a significant health challenge.
- Investigating natural compounds like Diosgenin for anti-cancer properties is crucial.
Purpose of the Study:
- To elucidate the mechanism of action of Diosgenin against gastric cancer (GC).
- To identify key molecular targets and pathways involved in Diosgenin's anti-GC effects.
Main Methods:
- Utilized multi-omics data from six databases and enrichment analysis.
- Employed weighted gene co-expression network analysis (WGCNA) for GC-related genes.
- Integrated bioinformatics, single-cell RNA sequencing, Mendelian randomization, and cell experiments.
Main Results:
- Identified 605 Diosgenin targets, enriched in cell apoptosis, TNF signaling, and platinum resistance pathways relevant to GC.
- Diosgenin targets 311 genes involved in cell cycle, p53, and FoxO signaling pathways.
- Diosgenin inhibited GC cell proliferation, migration, and invasion, suppressing PLK1 and MDM2 while upregulating p53.
Conclusions:
- Diosgenin demonstrates significant anti-gastric cancer activity.
- Diosgenin's therapeutic potential lies in its ability to modulate key cancer-related pathways and proteins.
- Findings support Diosgenin as a promising agent for future GC research and clinical applications.
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