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.

Serum anti-SPP1 autoantibody as a potential novel biomarker in detection of esophageal squamous cell carcinoma

“…6 (See legend on previous page.) signaling pathway in tongue cancer [33]. Besides, high expression of SPP1 is correlated with poor survival in several cancers [34,35].…”

“…SPP1-CD44 axis could promote cancer stemness in pancreatic cancer [ 32 ]. It was reported that lacking of SPP1 inhibits progression by mediating the PI3K/Akt signaling pathway in tongue cancer [ 33 ]. Besides, high expression of SPP1 is correlated with poor survival in several cancers [ 34 , 35 ].…”

Comprehensive analysis of potential cellular communication networks in advanced osteosarcoma using single-cell RNA sequencing data

“…In addition, previous research found inhibition of the SPP1 gene may have therapeutic benefits for tongue cancer and may be a useful target for therapy (Zhang et al, 2020). Moreover, in pancreatic tumor microenvironment factors, the SPP1-CD44 axis can promote cancer stemness (Nallasamy et al, 2021).…”

“…In colorectal cancer (CRC), SPP1 was highly upregulated and increased CRC metastasis by promoting epithelial-mesenchymal transition (EMT) ( Xu et al, 2017 ). In addition, previous research found inhibition of the SPP1 gene may have therapeutic benefits for tongue cancer and may be a useful target for therapy ( Zhang et al, 2020 ). Moreover, in pancreatic tumor microenvironment factors, the SPP1-CD44 axis can promote cancer stemness ( Nallasamy et al, 2021 ).…”

Comprehensive Analysis to Identify SPP1 as a Prognostic Biomarker in Cervical Cancer

“…Thus, it is necessary to find more accurate biomarkers to detect at an early stage and monitor disease progression. According to the previous studies, SPP1 is overexpressed in various cancer types ( Xu et al (2017) ; Choe et al (2018) ; Zhang et al (2020) ) and identified as a prognostic factor ( Li et al (2018) ; Chen J et al (2019) ; Guo et al (2020) ), while to our knowledge, no study has explored the relationship of SPP1 expression and cervical cancer. In our study, we attempted to explore the potential mechanism of SPP1 in promoting cervical cancer and its feasibility as a molecular biomarker.…”