Comprehensive and Integrated Analysis Identifies ZEB1 as a Key Novel Gene in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer with a poor prognosis. Therefore, it is crucial to explore molecular prognostic biomarkers for OSCC. ZEB1 (also known as δEF1) is a member of the zinc finger E-box binding protein family of transcription factors involved in various biological processes, including tumorigenesis, progression, and metastasis. Recent evidence suggests that ZEB1 has a role in the tumorigenicity of oral epithelial cells, although its mode of action needs to be investigated further. To better understand the relationship between ZEB1 and OSCC, we transfected the ZEB1-overexpressing oral squamous cell lines SCC9 and SCC25 with lentivirus and then extracted RNA from the cells for gene expression analysis. Furthermore, the GSE30784 dataset was downloaded from the Gene Expression Omnibus (GEO) database to identify potential biomarkers of OSCC and to assess the potential mechanisms. The criteria for identification of their DEGs were |logFC| > 1 and P < 0.05. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analyses were also carried out. Integrating the data from the PPI network and survival analysis identified that ZEB1 might be an independent prognostic biomarker in OSCC. In conclusion, integrated bioinformatics and microarray analysis identified the critical gene ZEB1 linked to the overall survival (OS) of patients with OSCC. ZEB1 could be applied as a prognostic biomarker to forecast the survival of patients with OSCC and might indicate innovative therapeutic indicators for OSCC.

The role of MAPK signaling pathway in formation of EMT in oral squamous carcinoma cells induced by TNF-α.

To study the role of MAPK signaling pathway in the development of Epithelial-mesenchymal transition in oral squamous cell carcinoma induced by inflammatory factor TNF-α. After the action of TNF-α, the expression of JNK, ERK, P38 in MAPK signaling pathway increased and the expression of E-cadherin, Claudin1 decreased significantly compared to the normal control group. After the addition of corresponding inhibitor, the expression of JNK, ERK, P38 decreased and the expression of E-cadherin, Claudin1 increased compared with TNF-α group. TNF-α regulated the role of EMT in promoting the invasion and metastasis of oral squamous carcinoma cells through MAPK signaling pathway.

Snail interacts with Id2 in the regulation of TNF-α-induced cancer cell invasion and migration in OSCC.

The inflammatory tumor microenvironment has been identified to play a pivotal role in tumor development and metastasis. Tumor necrosis factor-α (TNF-α) is one of the key cytokines that regulate the inflammatory processes in tumor promotion. In the current study, we treated three oral squamous cell carcinoma (OSCC) cell lines with TNF-α to study its role in inflammation-induced tumor progression. Here we show that TNF-α induces stabilization of the transcriptional repressor Snail and activates NF-κB pathway in the three OSCC cell lines. These activities resulted in the increased motility and invasiveness of three OSCC cell lines. In addition, upon dealing with TNF-α for the indicated time, three OSCC cell lines underwent epithelial-to-mesenchymal transition (EMT), in which they presented a fibroblast-like phenotype and had a decreased expression of epithelial marker (E-cadherin) and an increased expression of mesenchymal marker (vimentin). We further demonstrated that TNF-α can up-regulate the expression of Id2 while inducing an EMT in oral cancer cells. Finally, we showed that Id2 interacted with Snail which may constrain Snail-dependent suppression of E-cadherin. In conclusion, our study indicates that TNF-α induces Snail stabilization is dependent on the activation of NF-κB pathway and results in increasing cell invasion and migration in OSCC cells. Id2 may contribute to regulate the function of Snail during TNF-α-mediated EMT in OSCC. These findings have significant implications for inflammation-induced tumor promotion in OSCC.

Zinc dependent endopeptidases of matrix metalloproteinases-9 expressions is associated with tumor metastases of oral squamous cell carcinoma in Chinese population: a meta-analysis.

Matrix metalloproteinase-9 (MMP-9) is an important member of zinc dependent endopeptidases family and is considered to be involved in the invasion and metastasis of cancer cells. Many studies were published to assess the prognostic role of MMP-9 expression in patients with oral squamous cell Carcinoma, but the findings from those studies were inconsistent in Chinese population. We searched eligible studies in Pubmed, Embase, and Web of Science databases. Six studies with a total of 556 patients were finally included into the meta-analysis. The pooled odds ratios (OR) with the corresponding 95% confidence interval (95% CIs) for positive rate of MMP-9 were calculated by using meta-analysis. Overall, MMP-9 positive expression was associated with tumor metastases in patients with oral squamous cell Carcinoma (fixed-effects OR 4.24, 95% CI 2.25-7.99, P < 0.001; random-effects OR 4.35, 95% CI 2.31-8.21, P < 0.001). Our results indicated that MMP-9 expression is associated with tumor metastases in patients with oral squamous cell carcinoma, and patients with higher MMP-9 expression have less tumor metastases.

[Evaluation of a model of temporomandibular disorders established by transzygomatic arch traction of the mandibular ramus in rabbits].

OBJECTIVE: To evaluate a model of temporomandibular disorders established by transzygomatic arch traction of the mandibular ramus in rabbits. METHODS: Fifteen adult New Zealand rabbits were subjected to traction in the postero-superior direction unilaterally using elastic force and six rabbits used as the control. Histopathologic change of the disc, joint space and cartilage was observed through Hematoxylin and Eosin staining. RESULTS: Anterior disc displacement or disc deformity in four experimental rabbits was observed on the traction side 2 weeks after operation. At 4 weeks, fibrous adhesions in joint compartment were found in five experimental rabbits. The condyles or articular eminences of some experimental rabbits showed irregularities on the cartilage surface. In the 6 th week, bad disc deformity in four rabbits and severe fibrous adhesions in five rabbits was observed on the traction side, and subchondralbone and calcified cartilage became irregular. In control group, All articular structures were normal. CONCLUSIONS: A animal model of temporomandibular disorders can be established by transzygomatic arch traction of the mandible.