Mechanistic Exploration of Aristolochic Acid I-Induced Hepatocellular Carcinoma: Insights from Network Toxicology, Machine Learning, Molecular Docking, and Molecular Dynamics Simulation
Abstract
1. Introduction
2. Results
2.1. Toxicity Prediction for AAI
2.2. Search of Targets for AAI and HCC
2.3. Recognition Core Gene from GEO
2.4. Genetic Screening Based on Machine Learning
2.5. Construction of Protein–Protein Interaction Network and Hub Targets Screening
2.6. GO and KEGG Enrichment Analysis
2.7. Immunoinfiltration and Drug Sensitivity Analysis
2.8. Survival Analysis
2.9. Molecular Docking
2.10. Molecular Dynamics Simulations
2.11. Immunohistochemistry Based on the HPA Database
3. Discussion
4. Conclusions
5. Methods and Materials
5.1. Study Design
5.2. Forecasting Toxicity Effects of AAI
5.3. Search for AAI Targets
5.4. Identification of Targets Associated with HCC
5.5. Recognition of Core Genes from GEO
5.6. Machine Learning Powered Genetic Assessment
5.7. Construction of Protein–Protein Interaction Network
5.8. Hub Target Screening
5.9. Functional Enrichment Profiling via GO and KEGG
5.10. Immuneinfiltration and Drug Sensitivity Analyses
5.11. Survival Analysis Using Samples from the TCGA Database
5.12. Molecular Docking of AAI and Its Core Targets
5.13. Molecular Dynamics Simulations for Core Genes
5.14. Immunohistochemistry Validation Form HPA Database
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Tu, T.; Zheng, T.; Lin, H.; Cheng, P.; Yang, Y.; Liu, B.; Ying, X.; Xie, Q. Mechanistic Exploration of Aristolochic Acid I-Induced Hepatocellular Carcinoma: Insights from Network Toxicology, Machine Learning, Molecular Docking, and Molecular Dynamics Simulation. Toxins 2025, 17, 390. https://doi.org/10.3390/toxins17080390
Tu T, Zheng T, Lin H, Cheng P, Yang Y, Liu B, Ying X, Xie Q. Mechanistic Exploration of Aristolochic Acid I-Induced Hepatocellular Carcinoma: Insights from Network Toxicology, Machine Learning, Molecular Docking, and Molecular Dynamics Simulation. Toxins. 2025; 17(8):390. https://doi.org/10.3390/toxins17080390
Chicago/Turabian StyleTu, Tiantaixi, Tongtong Zheng, Hangqi Lin, Peifeng Cheng, Ye Yang, Bolin Liu, Xinwang Ying, and Qingfeng Xie. 2025. "Mechanistic Exploration of Aristolochic Acid I-Induced Hepatocellular Carcinoma: Insights from Network Toxicology, Machine Learning, Molecular Docking, and Molecular Dynamics Simulation" Toxins 17, no. 8: 390. https://doi.org/10.3390/toxins17080390
APA StyleTu, T., Zheng, T., Lin, H., Cheng, P., Yang, Y., Liu, B., Ying, X., & Xie, Q. (2025). Mechanistic Exploration of Aristolochic Acid I-Induced Hepatocellular Carcinoma: Insights from Network Toxicology, Machine Learning, Molecular Docking, and Molecular Dynamics Simulation. Toxins, 17(8), 390. https://doi.org/10.3390/toxins17080390