Retinoic Acid Inhibits Oral Squamous Cell Carcinoma Through Multitarget Mechanisms

To investigate the potential mechanism of Retinoic Acid (RA) in inhibiting Oral Squamous Cell Carcinoma (OSCC). RA targets were predicted using Swiss Target Prediction and STITCH databases. OSCC-related targets were obtained from GeneCards, OMIM and TTD databases. Shared drug-disease targets were analyzed using STRING database to identify core targets and construct protein-protein interaction (PPI) networks. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the DAVID database. Molecular docking between RA and target proteins was conducted with AutoDock Vina 1.1.2. We identified 200 RA targets and 6,463 OSCC-related targets, yielding 166 shared targets included STAT3, EP300, ESR1, TP53, MYC, HDAC1, CTNNB1, JUN, CREBBP and IL6. GO analysis revealed 61 cellular components, 688 biological processes and 118 molecular functions, with KEGG pathway enrichment identifying thyroid hormone signaling, IL-17 signaling, AGE-RAGE signaling and PI3K-Akt signaling as significant pathways. Molecular docking showed SRC, STAT3, P300, MAPK1, HDAC2, CREBBP and HDAC1 as potential targets. RA exhibits anti-OSCC effects through multi-target and multi-pathway mechanisms, particularly in regulating cell proliferation, differentiation and apoptosis.