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IntroductionMethodsResultsDiscussionHuman oral squamous cell carcinoma (OSCC) is the most common type of oral cancer and has a poor survival rate. Cell-cell communication between OSCC cells and cancer-associated fibroblasts (CAFs) plays important roles in OSCC progression. We previously demonstrated that CAFs promote OSCC cell migration and invasion. However, how OSCC cells influence CAFs proliferation is unknown.Knockdown of PVT1 was confirmed using lentivirus infection technique. CAFs in tissues were identified by staining the cells with α-SMA using immunohistochemical technique. CCK-8 assay was used to evaluate cell proliferation. The mRNA level of a gene was measured by qRT-PCR. Secreted TGF-β were detected using ELISA assay.We found that knockdown of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was associated with a low density of CAFs in xenograft tumors in mice; further analysis revealed that PVT1 in OSCC cells induced CAF proliferation through transforming growth factor (TGF)-β.Our results demonstrate that lncRNA PVT1 in tumor cells participates in CAF development in OSCC by regulating TGF-β. This study revealed a new mechanism by which PVT1 regulates OSCC progression and PVT1 is a potential therapeutic target in OSCC [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the head and neck, and among the OSCCs, tongue squamous cell carcinoma (TSCC) is one of the most common types. Although therapy strategies have recently advanced, the prognosis of TSCC has not substantially improved. Metastasis is one of the main causes of patient mortality in TSCC; therefore, it is necessary to elucidate the mechanism by which TSCC metastasis is regulated. In the present study, the early growth response 1 (Egr-1) expression in TSCC was analyzed based on GEO datasets and the effect of Egr-1 in TSCC tumor cell migration and invasion was measured using Transwell assay. By overexpressing dual-specificity protein phosphatase 1 (DUSP1) in cells with Egr-1 knockdown using lentivirus infection, the role of DUSP1 in Egr-1-regulated TSCC cell migration and invasion was determined. By using luciferase and ChIP assays, the mechanism behind how DUSP1 is regulated by Egr-1 was detected. In the present study, it was demonstrated that Egr-1 was downregulated in TSCC and the knockdown of Egr-1 increased TSCC cell migration and invasion. The expression of Egr-1 was also correlated with DUSP1. The overexpression of DUSP1 in Egr-1 knockdown cells, reduced the level of cell migration and invasion. Furthermore, it was demonstrated that knockdown of Egr-1 inhibited the promoter activity of DUSP1 and the site through which Egr-1 regulates DUSP1 transcription was identified. In conclusion, the present study demonstrated that Egr-1 regulates TSCC cell migration and invasion through modulating DUSP1, suggesting the potential of Egr-1 and DUSP1 as therapy targets for TSCC. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is one of the most common squamous cell carcinomas of the head and neck. The morbidity and mortality rates of OSCC have increased in recent years. However, the pathogenesis of this disease remains unknown. The present study aimed to identify predictive biomarkers and therapeutic targets for OSCC. Bioinformatics screening of differentially expressed genes in OSCC was performed based on data from The Cancer Genome Atlas and Gene Expression Omnibus databases. Dickkopf Wnt signaling pathway inhibitor 1 (DKK1) was identified to be associated with survival, tumor immunity and DNA repair in OSCC. Furthermore, the effects of DKK1 were evaluated by the knockdown of DKK1 in two OSCC cell lines. The proliferation, clonogenicity, migration and invasion of the cells were assessed in vitro using Cell Counting Kit-8, colony formation, wound healing and Transwell assays, respectively, and were found to be inhibited by DKK1 knockdown. The present study suggests that DKK1 may be used in the prognosis of patients with OSCC and that targeting DKK1 is a potential strategy for OSCC therapy. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC), one of the most common malignant tumors, endangers human health. Recently, the incidence of HNSCC has kept increasing: However, its prognosis has not significantly improved. Understanding the molecular mechanism underlying HNSCC development will therefore provide new strategies for therapy. The present study attempted to identify differentially expressed (DE) long non-coding (lnc)RNAs and investigated their functional role in HNSCC development. Expression profiles of HNSCC and normal samples were downloaded from The Cancer Genome Atlas (TCGA) database. DElncRNAs between the HNSCC and normal samples were highlighted and their potential functions were investigated through lncRNA-micro (mi)RNA-mRNA network by using Gene Expression Profiling Interactive Analysis, UALCAN, DIANA-LncBase v.2 and miRWalk 3.0 databases. A total of 343 dysregulated lncRNAs were identified. Among these DElncRNAs, CTD-2357A8.3 had the highest fold-change and was significantly associated with poor overall survival in patients with HNSCC. Furthermore, CTD-2357A8.3 was associated with 'signaling pathways regulating stem cell pluripotency', 'proteoglycans in cancer', 'transcriptional misregulation in cancer' and 'chemokine signaling pathway'. Further analysis demonstrated that CTD-2357A8.3 acted as a 'sponge' in order to competitively adsorb miRNA to regulate the expression of target gene caveolin 1 (CAV1) in HNSCC. In conclusion, CTD-2357A8.3 may be considered a promising diagnosis biomarker or a therapeutic target for the treatment of HNSCC. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors that endanger human health. In recent years, the incidence of HNSCC has been increasing, without any significant improvement in the prognosis. Therefore, increased knowledge on the molecular mechanism underlying HNSCC development will allow the development of new strategies for therapy. The present study attempted to identify key genes involved in HNSCC development. Expression profiles of HNSCC and normal samples were downloaded from The Cancer Genome Atlas database. Differentially expressed genes (DEGs) between the HNSCC and normal samples were identified and subjected to Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis. A protein-protein interaction (PPI) network was constructed, and Cytoscape CentiScape and Gene Expression Profiling Interactive Analysis were used to identify key DEGs. Finally, expression profiles of HNSCCs, including 500 HNSCCs and 44 normal samples, were included in the analysis. A total of 1,181 DEGs were screened, among which 354 genes were upregulated and 827 genes were downregulated in HNSCC compared with normal tissues. The GO enrichment analysis showed that the DEGs were mainly involved in chloride transmembrane transporter, metalloendopeptidase and substrate-specific channel activities. The KEGG pathway analysis revealed that the DEGs were mainly associated with 'protein digestion and absorption', as well as 'extracellular matrix-receptor interaction'. Integrin α-5 (ITGA5) was identified as a hub gene, based on the PPI network complex, and was confirmed to be significantly associated with the overall survival rate. Moreover, ITGA5 was overexpressed specifically in HNSCC. The genes found, notably ITGA5, are potential diagnostic biomarkers and therapeutic targets in HNSCC. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is one of the most common types of malignant head and neck tumor, which poses a serious threat to human health. In recent years, the incidence of OSCC has been increasing, while the prognosis has not significantly improved. Elucidation of the molecular mechanisms underlying the development of OSCC may provide novel therapeutic strategies. In the present study, the gene expression profiles from 4 datasets, including 244 OSCC and 95 normal oral mucosa samples, were subjected to statistical and Bioinformatics analysis. A total of 34 differentially expressed genes (DEGs) were identified, among which 14 were upregulated and 20 were downregulated in OSCC compared with normal oral mucosa tissues. Gene Ontology enrichment analysis indicated that the DEGs were mainly involved in regulation of the immune response, cell adhesion and cell proliferative processes. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were mainly associated with the phosphoinositide-3 kinase Akt and Toll-like receptor signaling pathway. The key candidate DEGs were identified from the complex protein-protein interaction network, and secreted phosphoprotein 1 (SPP1), integrin subunit α 3 and plasminogen activator, urokinase (PLAU) were confirmed to be significantly associated with the survival rate. Cell Counting Kit-8 and Transwell assays demonstrated that SPP1 and PLAU regulate cell proliferation, migration and invasion. The candidate genes/pathways identified in the present study may include promising diagnostic biomarkers or therapeutic targets for OSCC. [ABSTRACT FROM AUTHOR]

Abstract CDKL1 is a cyclin-dependent kinase-like kinase that is highly expressed in diverse types of cancer cells. However, the role of CDKL1 in the chemoresistance of oral squamous cell carcinoma (OSCC) remains largely undefined. Here, we explored the role of CDKL1 in the chemoresistance of the human OSCC cell line CAL27 to hydroxycamptothecin (HCPT). Real-time quantitative polymerase chain reaction and western blotting revealed that exposure of CAL27 cells to HCPT led to a marked increase in the expression of CDKL1 at the mRNA and protein levels. Knockdown of CDKL1 significantly suppressed cell proliferation and induced cell cycle G0/G1 phase arrest in CAL27 cells based on the results of MTT and flow cytometry assays, respectively. CAL27 cells displayed attenuated biological activity of the cell population. After treatment with HCPT, whereas CDKL1 overexpression increased the resistance to HCPT of the remaining cells. Moreover, the western blot showed that the expression of cleaved-caspase 3 and phosphorylated ataxia telangiectasia mutated proteins was upregulated by HCPT treatment in CAL27 cells. Furthermore, CDKL1 overexpression partially reversed the inhibitory effects of HCPT in CAL27 cells. These results suggest that CDKL1 overexpression decreased the chemosensitivity of OSCC cells to HCPT, indicating a potential strategic approach for reversing the HCPT resistance in human OSCC. Highlights • The role of CDKL1 in the chemoresistance of the human OSCC cell line CAL27 to hydroxycamptothecin (HCPT). • Exposure of CAL27 cells to HCPT led to a marked increase in the expression of CDKL1. • Attenuated proliferation activity after treatment with HCPT. • CDKL1 overexpression increased the resistance to HCPT of the remaining cells. • CDKL1 overexpression partially reversed the inhibitory effects of HCPT in CAL27 cells. • CDKL1 overexpression decreased the chemosensitivity of OSCC cells to HCPT. [ABSTRACT FROM AUTHOR]

Objective Squamous cell carcinoma is often associated with the deletion or mutation of zinc finger protein 750 (ZNF750), its deletion or mutation is associated with squamous epithelial malignant biological characteristics. The present study is to explore the mechanism of ZNF750 to suppress the tumor malignant process by regulation tumor microenvironment. Methods To evaluate the changes of tumor microenvironment in oral squamous cells carcinoma cell line CAL-27 cell, the expression of angiogenin, vascular endothelial growth factor (VEGF), prolyl hydroxylase 2 (PHD2), G protein signal regulated protein 5 (RGS5), integrin A5 (ITGA5), integrin B1 (ITGB1) and CD44 were detected by Western-blot. The changes of platelet derived growth factor (PDGFB) and tumor vascular marker CD105 (Endoglin) mRNA were estimated by qPCR. The effect of over-expressed ZNF750 on cell viability and lateral migration capacity was investigated by CCK-8 and cell scratch assay in three oral squamous cells carcinoma. Results ZNF750 could effectively inhibit the protein or mRNA expression of angiogenin, VEGF, RGS5 and CD105, repressed the cell adhesion molecules ITGA5, ITGB1 and CD44, but up-regulate the protein or mRNA expression of PHD2 and PDGFB. The cell viability and lateral migration ability of three oral squamous cells carcinoma were reduced by over-expression of ZNF750. Conclusion ZNF750 could modulate the tumor vascular microenvironment to inhibit the oral squamous cells carcinoma malignant progression. [ABSTRACT FROM AUTHOR]

Summary Objectives miR-29b has been implicated in various cancers. However, the role of miR-29b in tongue squamous cell carcinoma (TSCC) remains unclear. This study aimed to investigate the role of miR-29b in TSCC progression. Materials and methods The expression of miR-29b was analyzed in TSCC tissues and cells. Functional studies were performed in TSCC cells. Real time-PCR, Western blot, cell proliferation, transwell, and dual luciferase reporter assays were performed according to standard procedures. Results miR-29b was significantly decreased in TSCC specimens and cell lines compared with corresponding normal counterparts. Overexpression of miR-29b significantly inhibited the proliferation, migration, invasion, and cell-cycle progression of TSCC cells, and promoted apoptosis. Moreover, miR-29b targeted the 3′ untranslated region of the Sp1 transcript and resulted in the deregulation of Sp1. The inhibition of Sp1 by miR-29b subsequently resulted in the upregulation of PTEN, leading to a decline of phosphorylated AKT. Knockdown of Sp1 in TSCC cell lines mimicked the effects of miR-29b overexpression. In addition, the expression of miR-29b was inversely correlated with Sp1 and positively correlated with the PTEN in TSCC specimens. Conclusion miR-29b functions as a tumor suppressor in TSCC, and the miR-29b/Sp1/PTEN/AKT axis might represent a potential therapeutic target for TSCC intervention. [ABSTRACT FROM AUTHOR]

Gene fusion is caused by the linkage of previously separate genes or sequences. Recently, an increasing number of novel fusion genes have been identified and associated with tumor progression, and several of them have been suggested as promising targets for tumor therapy. However, there are hardly any studies reporting the association of fusion genes with the progression of oral squamous cell carcinoma (OSCC). In this study, we identified a total of 11 fused genes in OSCC cells. We further analyzed the structure of one fused gene, TRIM52-RACK1, and detected its function in tumor progression in vitro. We found that TRIM52-RACK1 was caused by a deletion of 181,257,187-181,247,386 at 5q35.3 and it promoted OSCC cell proliferation, migration, and invasion. Therefore, TRIM52-RACK1 can be a promising target for tumor therapy in OSCC. • Eleven fused genes were found in OSCC cells. • Fused gene, TRIM-RACK1, was caused by the deletion of 181,257,187-181,247,386 at 5q35.3. • TRIM52-RACK1 promotes OSCC cells proliferation, migration and invasion. [ABSTRACT FROM AUTHOR]