Expression and influence of Notch signaling in oral squamous cell carcinoma

Notch signaling dysregulation plays an important role in altering cancer cell behaviors; however, its role in oral squamous cell carcinoma (OSCC) remains controversial. This study aimed to investigate the role of Notch signaling related genes in human OSCC using a meta-analysis of Gene Expression Omnibus database (GEO-publicly available gene expression microarray data) and to examine the role of Notch signaling in OSCC behaviors. The meta-analysis included 13 GEO datasets and was performed by combining effect sizes in a random effect model. The results demonstrated that in OSCC dysregulated genes participated in the metabolic process and protein binding as determined by gene ontology analysis. Enriched pathway analysis demonstrated the majority of the dysregulated genes were involved in pathway categories as follow; pathway in cancers, small cell lung cancer, extracellular matrix-receptor interaction, focal adhesion, and cell cycle progression. Interestingly, the enriched pathway analysis also demonstrated that OSCC samples exhibited an upregulation of genes in Notch signaling pathway, namely JAG1, JAG2, ADAM17, NCSTN, PSEN1, NCOR2, NUMB, DVL3, HDAC1, and HDAC2. Furthermore, Notch signaling inhibition by a gamma-secretase inhibitor significantly decreased OSCC cell proliferation in vitro, corresponding with a decrease in C-FOS mRNA expression. The study demonstrated that Notch signaling is dysregulated in human OSCC and plays a role in cell proliferation.