Potential effect of MSR1 and C6 ceramide small molecules on nasopharyngeal carcinoma based on GSEA analysis

Abstract

Purpose: To investigate some potential therapeutic agents and targets for nasopharyngeal carcinoma (NPC). Methods: Some potential therapeutic agents and target genes for NPC were identified by integrating bioinformatic analysis and in vitro experimental validation. Three datasets of NPC patients were gathered to reveal 26 upregulated and 344 downregulated differentially expressed genes (DGEs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analysis (KEGG) of the DGEs were implemented. Separately, 316 drug and small molecule target genes were acquired from the SEA database, allowing for detection of C6-ceramide as a small molecule of high relevance to NPC. Then, the differentially upregulated genes were intersected with potential target genes of C6-ceramide small molecules to obtain macrophage scavenger receptor 1 (MSR1). Finally, the study validated the potential roles of MSR1 and C6-ceramide in NPC cell lines. Results: Knockdown of MSR1 expressions in NPC cells significantly decreased cell viability. Treatment with 10 μmol/L C6-ceramide also significantly reduced NPC cell viability (p < 0.0001). Furthermore, C6-ceramide attenuated the increase in MSR1 levels induced by MSR1 overexpression in NPC cells (p < 0.0001). Concurrently, MSR1 knockdown decreased expression of PI3K and AKT, while MSR1 overexpression upregulated AKT and PI3K levels. Conclusion: MSR1 modulates viability of NPC cells by regulating PI3K and AKT expression. Additionally, C6-ceramide exerts therapeutic effect on NPC by regulating MSR1 expression. These findings reveal new therapeutic targets and strategies for the clinical management of NPC. These results establish a rationale for further exploration of MSR1 and ceramides as novel targets in NPC.