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Network-Based Method to Investigate the Promoted Cell Apoptosis Mechanisms of Oridonin in OSCC through the
Guohui Wu1,2, Yusheng Guo1, Yang Liu3
1School of Clinical Medicine, Guangdong Pharmaceutical University, Guangzhou 510000, China.
Abstract:
The morbidity of oral cancer is high in the world. Oridonin is a traditional Chinese medicine that can effectively inhibit oral squamous cell carcinoma (OSCC) growth, but its mechanism remains unclear. Our previous data showed that oridonin inhibited CAL-27 cell proliferation and promoted apoptosis. Herein, we explored the mechanism and target of oridonin in human OSCC through RNA sequencing and integration of multiple bioinformatics analysis strategies. Differences in gene expression can be analyzed with RNA sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), gene set enrichment analysis (GSEA), Disease Ontology (DO), and other enrichment analyses were used to evaluate differentially expressed genes (DEGs). Protein-protein interaction (PPI) networks were built via the STRING database. It was found that tumor necrosis factor (TNF) signaling pathway, cytokine-cytokine receptor interaction, and nuclear factor-kappa B (NF-kappaB) signaling pathway were associated with the therapeutic effects of oridonin in OSCC. Three key genes (BIRC3, TNFSF10, and BCL6) were found to associate with cell apoptosis in OSCC cells treated with oridonin. Quantitative PCR assays verified the expression of apoptosis-related DEGs: TNFSF10, BIRC3, AIFM2, BCL6, BCL2L2, and Bax. Western blots were employed for verifying proteins expression associated with DEGs: cleaved caspase 3, Bax, Bcl-w, anti-cIAP2, and anti-TRAIL. In conclusion, our findings reveal the molecular pathways and targets by which oridonin can treat and induce cytotoxic effects in OSCC: by affecting the signaling including TNF, NF-κB, and cytokine-cytokine receptor interaction and by regulating the key gene BIRC3, TNFSF10, and BCL6. It should be noted that further clinical trial validation is very necessary. Combined with current research trends, our existing research may provide innovative research drugs for the treatment of OSCC.
Insights
Oridonin, a traditional Chinese medicine, effectively inhibits oral squamous cell carcinoma (OSCC) by impacting tumor necrosis factor (TNF) and nuclear factor-kappa B (NF-κB) signaling pathways. It also regulates key genes like BIRC3, TNFSF10, and BCL6, inducing cancer cell death.
Area of Science:
- Oncology
- Pharmacology
- Bioinformatics
Background:
- Oral cancer, specifically oral squamous cell carcinoma (OSCC), presents a significant global health challenge with high morbidity.
- Oridonin, a component of traditional Chinese medicine, demonstrates potential in inhibiting OSCC progression, but its precise therapeutic mechanisms require elucidation.
Purpose of the Study:
- To investigate the molecular mechanisms and identify therapeutic targets of oridonin in human OSCC.
- To analyze gene expression profiles and construct interaction networks to understand oridonin's effects on OSCC cells.
Main Methods:
- RNA sequencing was employed to analyze gene expression differences in OSCC cells treated with oridonin.
- Bioinformatics strategies, including KEGG, GO, GSEA, and DO analyses, were used to evaluate differentially expressed genes (DEGs).
- Protein-protein interaction (PPI) networks were constructed using the STRING database to identify key molecular players.
Main Results:
- Oridonin's therapeutic effects in OSCC are associated with the tumor necrosis factor (TNF) signaling pathway, cytokine-cytokine receptor interactions, and the nuclear factor-kappa B (NF-κB) signaling pathway.
- Three key genes—BIRC3, TNFSF10, and BCL6—were identified as crucial in mediating oridonin-induced apoptosis in OSCC cells.
- Quantitative PCR and Western blot analyses validated the expression of apoptosis-related genes and proteins, including cleaved caspase 3, Bax, and Bcl-w.
Conclusions:
- Oridonin exerts cytotoxic effects on OSCC by modulating TNF, NF-κB, and cytokine-cytokine receptor signaling pathways.
- The study identifies BIRC3, TNFSF10, and BCL6 as critical targets for oridonin's anti-OSCC activity.
- These findings offer a foundation for developing oridonin as an innovative therapeutic agent for OSCC, warranting further clinical validation.
