Silencing of SPP1 Suppresses Progression of Tongue Cancer by Mediating the PI3K/Akt Signaling Pathway

Abstract

Background: In the present study, we aimed to find an effective target for the treatment of tongue cancer using gene chip screening and signal pathway research. Methods: We used microarray screening and gene expression profile analyses to find important differentially expressed genes in tongue cancer. We constructed a protein-protein interaction network, and used enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes to screen for important genes. We then silenced the genes of interest in SCC154 cells to study the relationship with the Phosphatidylinositol 3-kinase/Akt signal pathway. Western blot analyses, the 3-(4,5Dimethylthiazol-yl)-2,5Dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) test, and immunofluorescence assays were used to compare the expression levels of Phosphatidylinositol 3-kinase/Akt signal pathway-related proteins, cell viability, and cell proliferation ability in normal SCC154 cells, Si-RNA SCC154 cells, and gene-silenced SCC154 cells. The scratch test, Transwell test, and western blotting were used to determine migration, invasion, and carcinogenesis. Results: Using GSE9844, GSE13601, and GSE31056 gene chips, we identified 93 upregulated genes and 76 downregulated genes in tongue cancer. Using the protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we further identified 47 differentially expressed genes. Using Kaplan-Meier plotter online tools, we also identified 3 genes (SPP1, Recombinant Human Secreted Phosphoprotein 1; PLAU, plasminogen activator urinary; and APP, amyloid precursor protein). Compared with normal SCC154 cells and Si-RNA control SCC154 cells, the expressions of Phosphatidylinositol 3-kinase/Akt pathway proteins in si-SPP1 SCC154 cells were significantly decreased (*P < 0.05), and the protein activities and proliferation abilities were also significantly decreased (*P < 0.05), while the migration ability, invasion ability, and cancer forming ability were significantly increased (*P < 0.05). Conclusion: Inhibition of the SPP1 gene may have a therapeutic effect on tongue cancer, and could be an effective target for the treatment of this disorder.