Bioinformatics Analysis of the Signaling Pathways and Genes of Gossypol Induce Death of Nasopharyngeal Carcinoma Cells.

Gossypol has been reported to exhibit antitumor effects against several human cancers. However, the anticancer effects of gossypol on nasopharyngeal carcinoma (NPC) have not been investigated. Against this backdrop, the present study was designed to evaluate the anticancer effects of gossypol against NPC cells and to identify the signaling pathways involved through bioinformatic analysis. Gossypol-inhibited death of NPC cells is concentration-dependent. To explore the underlying mechanism for gossypol's antitumor effect, microarray of gossypol-treated and -untreated NPC cells was performed. A total of 836 differentially expressing genes (DEGs) were identified in gossypol-treated NPC cells, of which 461 genes were upregulated and 375 genes were downregulated. The cellular components, molecular functions, biological processes, and signal pathways, in which the DEGs were involved, were identified by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The Gene Set Enrichment Analysis (GSEA) predicted upstream transcription factors (TF) ETS2 and E2F1 that regulate DEGs. Weighted Gene Co-expression Network Analysis (WGCNA) was performed to identify a class of modules and genes related to DNA repair and cell cycle. TNFRSF10B, a receptor for death in NPC cells, was knocked down. The results suggested that the ability of NPC cells to resist gossypol killing was enhanced. In addition, to further investigate the possible molecular mechanisms, we constructed a transcriptional regulatory network of TNFRSF10B containing 109 miRNAs and 47 TFs. Taken together, our results demonstrated that gossypol triggered antitumor effects against NPC cells, indicating its applicability for the management of NPC.