Oral squamous cell carcinoma (OSCC) represents one of the most common head and neck cancer that with dire prognosis due partly to the lack of reliable prognostic biomarker. Here, we aimed to develop a CpG site-based prognostic signature through which we could accurately predict overall survival (OS) of patients with OSCC. We obtained OSCC-related DNA methylation and gene expression data sets from the public accessible Gene Expression Omnibus. Correlations between methylation level of CpG sites and OS of patients with OSCC were assessed by univariate Cox regression analysis followed by robust likelihood-based survival analysis on those CpG sites with permutation P < 0.05 for further screening the optimal CpG sites for OSCC OS prediction based on the risk score formula that composed of the methylation level of optimal CpG sites weighted by their regression coefficients. Besides, differential expression genes (DEGs) and differential methylation genes (DMGs) in OSCC samples compared with normal samples were obtained and shared genes were considered as vital genes in OSCC tumorgenesis and progression. As a result, two CpG sites including cg17892178 and cg17378966 that located in NID2 and IDO1, respectively, were identified as the optimal prognostic signatures for OSCC OS. In addition, 12 overlapping genes between DEGs and DMGs that closely associated with inflammation or blood and tissue development-related biological processes were obtained. In conclusions, this study should provide valuable signatures for OSCC diagnosis and treatment. K E Y W O R D SDNA methylation, gene expression, oral squamous cell carcinoma, overall survival, prognosis

ObjectiveThe aim of this study was to explore the potential role and regulatory mechanism of microRNA (miR)‐222‐3p in oral squamous cell carcinoma (OSCC).MethodsThe expression level and prognostic significance of miR‐222‐3p was detected in OSCC tissues. CCK‐8, transwell, and flow cytometry assays were used to explore the effect of miR‐222‐3p on cell proliferation, migration, invasion, and apoptosis. The influence of miR‐222‐3p on cyclin‐dependent kinase inhibitor 1B (CDKN1B) expression was evaluated by luciferase assays, real‐time polymerase chain reaction, and Western blot.ResultsWe found that miR‐222‐3p was overexpressed in OSCC tissues, comparing with normal tissues. Kaplan‐Meier curves showed that OSCC patients with high expression of miR‐222‐3p (P = .003) showed worse overall survival than those patients with low expression of miR‐222‐3p. Multivariate analysis showed that miR‐222‐3p (P = .037) expression was an independent prognostic factor of OSCC patients. miR‐222‐3p promoted cell proliferation, migration and invasion and induced the apoptosis of SCC‐15 and Tca‐83 cells. Furthermore, luciferase reporter assays indicated that CDKN1B is targeted by miR‐222‐3p in OSCC cells. Overexpression of CDKN1B inhibited OSCC cell proliferation, migration, and invasion and promoted cell apoptosis rate.ConclusionsmiR‐222‐3p affects OSCC cell proliferation, migration, invasion, and apoptosis through targeting CDKN1B, and may be a potential prognostic biomarker for OSCC patients.

Oral squamous cell carcinoma (OSCC) has emerged as the most prevailing oral malignancy worldwide, characterized by cervical solid lymph node metastasis and strong local invasiveness. Overexpression of Transcription Factor AP-2 alpha (TFAP2A) is observed in a significant proportion of OSCC cases. In this study, we aimed to elucidate the function of TFAP2A in the progression of OSCC and the related molecular signaling pathways. The role of RELA was predicted using bioinformatics analysis. The mRNA abundances of RELA, TFAP2A, and β-catenin were assessed by Western blot and quantitative real-timePCR. The relationship between RELA, TFAP2A, and β-catenin and their correlation with clinicopathological characteristics of OSCC was evaluated. The target of RELA and TFAP2A was identified by the chromatin immunoprecipitation as well as luciferase reporter assay. The colony formation assay and MTS assay were performed to determine the proliferative level of OSCC cells. OSCC cell motility was determined by Transwell assay and wound-healing assay. The protein expressions of epithelial-mesenchymal transition-associated factors were evaluated by Western blot. The expressions of RELA and TFAP2A were elevated in OSCC, and their expressions displayed a positive correlation. The expression levels of RELA and TFAP2A were found to be associated with TNM staging and lymphatic metastasis of OSCC patients. RELA upregulation promoted OSCC progression, as manifested by increased levels of proliferation, invasion, and migration of OSCC cells. We also demonstrated that RELA was directly bound to the promoter of TFAP2A transcription, which activated multiple malignant and metastatic phenotypes.Furthermore, TFAP2A activated the Wnt/β-catenin signaling by targeting the promoter regions of β-catenin. The study found that RELA is critical for promoting the progression of OSCC via the RELA-TFAP2A-Wnt/β-catenin signaling pathway.The RELA-TFAP2A-Wnt/β-catenin signaling pathway is a potential target for reducing the aggressiveness of OSCC.

Background Although SCIRT has been reported to suppress breast cancer, its role in other cancers, such as oral squamous cell carcinoma (OSCC), is hardly known. We predicted that SCIRT might interact with miR‐221 to target lncRNA GAS5 and analyzed the interaction between SCIRT and miR‐221 in OSCC. Methods SCIRT and miR‐221 expression levels were quantified using RT‐qPCR. SCIRT subcellular localization was analyzed by subcellular fractionation assay. RNA pull‐down assay was applied to study the interaction between SCIRT and miR‐221. The role of SCIRT and miR‐221 in regulating GAS5 expression was analyzed by overexpression assay and RT‐qPCR. Cell apoptosis was analyzed by flow cytometry. Results SCIRT and GAS5 were downregulated, while miR‐221 was overexpressed in OSCC. SCIRT was detected in both nucleus and cytoplasm and directly interacted with miR‐221, while SCIRT overexpression failed to affect miR‐221 expression. In addition, GAS5 expression was increased by SCIRT and decreased by miR‐221. Moreover, SCIRT suppressed the role of miR‐221 in suppressing GAS5 expression and OSCC cell apoptosis. Conclusion SCIRT sponges miR‐221 to upregulate lncRNA GAS5 in OSCC and inhibit cancer cell apoptosis.

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