Network pharmacology and bioinformatics analysis on the underlying mechanisms of baicalein against oral squamous cell
1School of Stomatology, Dalian Medical University, Dalian, China.
Background And Aims:
This study performed a network pharmacology analysis to explore the potential anticancer activity of baicalein against oral squamous cell carcinoma (OSCC).
Methods:
The differentially expressed genes in OSCC were identified by the OSCC, and the key module related to OSCC was acquired by the weighted gene co-expression network analysis from GSE30784. Baicalein targets were obtained from GeneCards, SwissTargetPrediction and TCMSP (the traditional Chinese medicine systems pharmacology database and analysis platform) databases. Apart from GSE30784, OSCC-related genes were acquired from the Comparative Toxicogenomics Database and DisGeNET platform. The baicalein targets and OSCC-related genes were overlapped to acquire the drug-disease interaction genes. We input the candidate drug-disease interaction genes into the STRING database and created the protein-protein interaction network. The hub genes in the network were identified by cytoHubba. The expression levels of hub genes between cancer tissues and normal tissues were evaluated based on The Cancer Genome Atlas. Moreover, we performed the cancer immune infiltration analysis and evaluated the association between the expression of HIF1A and the abundance of infiltrating immune cells. The molecular docking between HIFA and baicalein was also performed and visualized. Additionally, the enrichment analysis was performed based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database.
Results:
After overlapping the candidate baicalein targets with OSCC-related genes, 34 candidate drug-disease interaction genes were obtained. cytoHubba identified the top 10 genes with high centrality measures from the network, including AKT1, CD44, EGFR, HIF1A, IGF1, MMP2, MYC, PTGS2, STAT3 and TP53. The enriched biological process terms included regulation of apoptotic signaling pathway, regulation of cysteine-type endopeptidase activity and cellular response to chemical stress. The top five enriched pathways comprised Kaposi sarcoma-associated herpesvirus infection, hepatitis C, p53 signaling pathway, Epstein-Barr virus infection and proteoglycans in cancer. The expression of HIF1A was positively associated with the infiltration levels of CD4 + T cells (cor = 0.131, p = 0.004) and dendritic cells (cor = 0.098, p = 0.03), whereas negatively associated with B cells (cor = -0.098, p = 0.03).
Conclusion:
Our results suggested that baicalein might be a candidate drug against OSCC. More studies are necessary to validate its anticancer effect and explore the underlying mechanisms.
Insights
Baicalein shows potential as an anticancer drug for oral squamous cell carcinoma (OSCC). Further research is needed to confirm its efficacy and mechanisms against OSCC.
Area of Science:
- Pharmacology
- Oncology
- Bioinformatics
Background:
- Oral squamous cell carcinoma (OSCC) is a significant global health concern.
- Baicalein, a natural compound, has shown promise in preliminary studies for its therapeutic potential.
- Understanding the molecular mechanisms of baicalein against OSCC is crucial for drug development.
Purpose of the Study:
- To investigate the potential anticancer activity of baicalein against oral squamous cell carcinoma (OSCC) using network pharmacology.
- To identify key molecular targets and pathways involved in baicalein's action on OSCC.
Main Methods:
- Network pharmacology analysis integrating gene expression data (GSE30784) and multiple databases (GeneCards, TCMSP, DisGeNET).
- Construction and analysis of protein-protein interaction networks to identify hub genes (e.g., HIF1A, AKT1, EGFR).
- Molecular docking, enrichment analysis (GO, KEGG), and cancer immune infiltration analysis.
Main Results:
- 34 drug-disease interaction genes were identified, with 10 hub genes highlighted.
- Enriched pathways included those related to apoptosis, viral infections, and cancer signaling.
- HIF1A expression correlated with immune cell infiltration, suggesting a role in the tumor microenvironment.
Conclusions:
- Baicalein demonstrates potential as a therapeutic agent for OSCC.
- The study provides a theoretical basis for baicalein's anticancer effects, warranting further experimental validation.
- Future research should focus on elucidating the precise mechanisms and clinical efficacy of baicalein in OSCC treatment.
