Abstract

Background: Hepatocellular carcinoma is the cancer with the highest mortality rate worldwide. Currently, existing treatments are not very effective for this disease. Different science areas have focused on developing new therapies, including nanomedicine. In-vitro studies have reported the anticancer activity of silver nanoparticles, particularly those coated with polyvinylpyrrolidone (AgNPs-PVP). Aims: Characterize the effect of AgNPs on the HepG2 by bioinformatics analysis. Methods: From a list of proteins, we performed in-silico analysis to predict protein-protein interaction, hub gene, gene ontology, KEGG pathways, hub gene expression, protein expression, survival, cell infiltration immune, and molecular docking of AgNPs-PVP to target proteins. Cytoscape and UCSF Chimera software, DAVID, UALCAN, TISIDB, and HDOCK databases were included in the predictive analysis. Results: Gene ontology and KEGG pathways showed that AgNP exposure causes cellular organelles dysregulation and deregulation of protein production mechanisms. Additionally, metabolic pathways were altered, including glycolysis, gluconeogenesis, and amino acid biosynthesis. Hub genes RPS15, RPLP0, EEF1B2, RPL12, and NACA showed differential expression for gene expression, protein, and survival analysis. Furthermore, RPS15 and RPL12 were positively correlated with CD8+ T cell infiltration, and RPLP0, EEF1B2, and NACA were negatively correlated with NK cell infiltration. Finally, molecular docking showed that AgNPs-PVP interacts highly with the target proteins. Conclusion: AgNPs cause alterations in cell viability. Furthermore, the deregulation of hub genes and the modulation of the immune system are associated with anticancer effects, and molecular docking demonstrated high interaction with the target proteins that should be studied experimentally.