Mechanism of Areca catechu L.inducing the transformation of oral submucous fibrosis to oral squamous cell carcinoma based on data mining and network pharmacology
Objective To explore the biological process of the transformation of oral submucosal fibrosis(OSF)into oral squamous cell carcinoma(OSCC)induced by Areca catechu L.,and lay a foundation for further validation as biomarkers and targets for precision medicine.Methods By applying bioinformatics analysis methods,pathogenic genes were obtained from GeneCards,OMI and DisGENET databases,and relevant action targets of Areca catechu L.active ingredients were obtained from TCMSP and Batman-TCM databases.Core targets were screened out for enrichment analysis based on the interaction network between active ingredients and targets.Pathological changes of OSCC and OSF were observed by hematoxylin-eosin staining and verified by Western blotting.Results In this study,24 active ingredients of Areca catechu L.were selected to participate in 101 key targets for promoting OSF progression to OSCC.Enrichment analysis showed 28 statistically significant pathways such as cell cycle,angiogenesis and epithelial-mesenchymal transition,and 17 functional classifications were annotated by protein clusters.The phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway with significant functional enrichment analysis was selected for verification based on literature reports.Western blotting analysis showed that OSCC/OSF+significantly increased the expression levels of PI3K and Akt compared with OSCC/OSF-(P<0.05).Conclusion The key molecules and targets of Areca catechu L.active ingredient in the progression from OSF to OSCC were initially screened out.The pathogenesis of OSCC was numerous and complex.PI3K/Akt pathway plays an important role in the pathological process of OSF transformation into OSCC,which may be a new target for early intervention or treatment.
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