An Integrated Analysis of RNA Sequencing and Molecular Docking Reveal EIF2AK2, IFIT1, and STAT1 as Key Targets of EGCG in Nasopharyngeal Carcinoma

Background:Epigallocatechin gallate (EGCG), a frequently studied catechin in green tea, has been shown to be involved in the antiproliferation and apoptosis of human Nasopharyngeal carcinoma (NPC) cells. However, the pharmacological targets and mechanism by which EGCG can combat NPC patients remain to be studied in detail. Methods:Experiments with cell lines and subsequent RNA sequencing, network pharmacology, molecular docking and molecular dynamics simulations were employed to elucidate the molecular mechanisms underlying the therapeutic effects of EGCG on NPC, with a focus on identifying potential therapeutic targets. Additionally, our assessment of the relationships between key target genes and NPC encompassed single-cell RNA sequencing (scRNA-seq) analysis as well as Mendelian Randomization (MR) analyses. Results:Analysis of the Gene Expression Omnibus (GEO) database and RNA sequencing of EGCG-treated NPC (HK-1) cells identified 165 potential targets associated with both EGCG and NPC. Network analysis using the STRING database and Cytoscape software revealed ten core targets, including EIF2AK2, IFIT1 and STAT1. KEGG pathway and Gene Ontology (GO) enrichment analyses highlighted key biological processes and signalling pathways involved in EGCG-mediated NPC treatment. Molecular docking simulations using AutoDock software confirmed strong binding interactions between EGCG and these core targets. Additionally, molecular dynamics simulations refined and validated the binding modes, providing a detailed molecular-level understanding. Finally, differential expression profiling of key target genes at the single-cell level demonstrated a concordance with transcriptomic data, while MR analyses validated the causal relationships between these target genes and the risk of NPC. Conclusion:These findings offer a theoretical basis for the molecular mechanisms underlying EGCG’s therapeutic effects on NPC. The identified core targets may serve as valuable references for drug development and functional additive research related to EGCG.