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Bioinformatics Analysis of the Signaling Pathways and Genes of Gossypol Induce Death of Nasopharyngeal Carcinoma Cells
- Source :
- DNA and Cell Biology. 40:1052-1063
- Publication Year :
- 2021
- Publisher :
- Mary Ann Liebert Inc, 2021.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Antineoplastic Agents
Cell Cycle Proteins
Biology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cell Line, Tumor
microRNA
otorhinolaryngologic diseases
Genetics
medicine
Humans
E2F1
Gene Regulatory Networks
KEGG
Molecular Biology
Gene
Transcription factor
Nasopharyngeal Carcinoma
Cell Death
Gossypol
Nasopharyngeal Neoplasms
Cell Biology
General Medicine
Cell cycle
medicine.disease
stomatognathic diseases
030104 developmental biology
Nasopharyngeal carcinoma
chemistry
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Cancer research
Transcriptome
Signal Transduction
Transcription Factors
Subjects
Details
- ISSN :
- 15577430 and 10445498
- Volume :
- 40
- Database :
- OpenAIRE
- Journal :
- DNA and Cell Biology
- Accession number :
- edsair.doi.dedup.....44b72733c52aaa2ebf6de535b010df37