RELA promotes the progression of oral squamous cell carcinoma via TFAP2A-Wnt/ß-catenin signaling.

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 ß-catenin were assessed by Western blot and quantitative real-timePCR. The relationship between RELA, TFAP2A, and ß-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/ß-catenin signaling by targeting the promoter regions of ß-catenin. The study found that RELA is critical for promoting the progression of OSCC via the RELA-TFAP2A-Wnt/ß-catenin signaling pathway. The RELA-TFAP2A-Wnt/ß-catenin signaling pathway is a potential target for reducing the aggressiveness of OSCC.

The role of long non-coding RNA LINC01296 in oral squamous cell carcinoma: a study based on bioinformatics analysis and in vitro validation.

Background: Oral squamous cell carcinoma (OSCC) is a common malignancy in the oral cavity that represents a significant global health problem. Multivariate analysis has shown that long non-coding RNA LINC01296 plays an important role in cancer biology. However, the functions of LINC01296 in OSCC are still unknown. Methods: The RNA profiles and clinicopathological information of OSCC patients and healthy subjects were downloaded. The expression level and prognostic value of LINC01296 were assessed. The functions and pathways of LINC01296were explored using the Gene Set Enrichment Analysis (GSEA) and functional analysis. The expression of LINC01296 in OSCC tissues and cell lines was determined by RT-qPCR. MTS assay was used to evaluate cell growth. The migration and invasion capacities of cells were assessed by wound healing assay and Transwell assay. Results: LINC01296 was overexpressed in the TCGA-OSCC datasets. High LINC01296expression was strongly correlated with poor outcomes of OSCC patients. LINC01296 was overexpressed in OSCC tissues compared with para-carcinoma tissues. Moreover, the expression of linc01296 was higher in CAL-27, HSC-2, and SCC-25 cells than in normal human oral keratinocytes (NHOKs). Functional analysis suggested that LINC01296might be involved in the regulation of the Wnt and MAPK signaling pathways. Additionally, LINC01296 deficiency suppressed the growth, migration, and invasion of OSCC cells, whereas overexpression of TFAP2A-AS1 cause opposite results. Conclusion: Our study showed that LINC01296 promoted OSCC cell growth, migration, and invasion, suggesting that LINC01296 might be a potential therapeutic target for OSCC.

LncRNA SCIRT absorbs miR-221 to advance the expression of lncRNA GAS5 in oral squamous cell carcinoma to inhibit cancer cell apoptosis.

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.

IncRNA ZNF667-AS1 Suppresses Epithelial Mesenchymal Transformation by Targeting TGF-ß1 in Oral Squamous Cell Carcinoma.

BACKGROUND: IncRNAs perform complex functions and play an essential role in all stages of tumor progression. However, there are few studies that discuss the function of lncRNA ZNF667-AS1in oral squamous cell carcinoma (OSCC). This study aimed at analyzing the expression and biological behavior of lncRNA ZNF667-AS1 in OSCC. METHODS: IncRNA ZNF667-AS1 expression level in OSCC tissues and cell lines was explored by real-time PCR. The role of lncRNA ZNF667-AS1 on prognosis was elucidated. Cell proliferation assay, plate colony formation assay, wound-healing assay, and transwell migration assay were used to detect cell proliferation ability, cell clone formation ability, migration ability, and invasion ability, respectively. The effect of lncRNA ZNF667-AS1 on epithelial mesenchymal transformation (EMT) process was evaluated by western blot and real-time PCR. RESULTS: The expression levels of lncRNA ZNF667-AS1 were decreased in malignant tumor tissues. The OSCC patients with high expression of lncRNA ZNF667-AS1 had a longer survival time. IncRNA ZNF667-AS1 inhibited cell proliferation, cell clone formation ability, invasion and migration. Furthermore, lncRNA ZNF667-AS1 could inhibit the EMT process by suppressing transforming growth factor-ß-1 (TGF-ß1) expression, and TGF-ß1 treatment could partially restore the inhibitory effect. CONCLUSIONS: IncRNA ZNF667-AS1 may act as an antioncogene inhibiting the ability of proliferation, cell clone formation, invasion and migration, and suppress the process of EMT by targeting TGF-ß1. IncRNA ZNF667-AS1 could be a potential therapeutic target and a new predictive biological marker of OSCC.

A Mixed-ligand Zn(II)-based Coordination Polymer for Selectively Detect 2,4,6-Trinitrophenol (TNP) and Treatment Effect on Periodontal Diseases via Inhibition Effect on P. gingivalis Growth.

A new difunctional Zn(II) coordination polymer (CP) with the chemical formula of [Zn(TBTA) (L)1.5]n (1) has been synthesized hydrothermally from tetrabromoterephthalic acid (H2TBTA) and 4,4'-bis(imidazole-1-yl)-biphenyl (L) ligands. Furthermore, due to its strong intense emission and open N donor sites, complex 1 could be used as a light-emitting sensor to determine 2,4,6-trinitrophenol (TNP) which has high selectivity and sensitivity. Furthermore, the anti-bacterial effect of the compound against P. gingivalis in vitro was evaluated by measuring the P. gingivalis growth curves after compound treatment. And the RT-PCR assay was performed to detect the relative expression of ragA and ragB, which are important for the P. gingivalis growth. The potential anti-infectious mechanism was further studied by using molecular docking technique.

MicroRNA-222-3p participates in the development of oral squamous cell carcinoma by targeting CDKN1B.

OBJECTIVE: The aim of this study was to explore the potential role and regulatory mechanism of microRNA (miR)-222-3p in oral squamous cell carcinoma (OSCC). METHODS: The 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. RESULTS: We 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. CONCLUSIONS: miR-222-3p affects OSCC cell proliferation, migration, invasion, and apoptosis through targeting CDKN1B, and may be a potential prognostic biomarker for OSCC patients.

A two-CpG-based prognostic signature for oral squamous cell carcinoma overall survival.

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.

Decreased absolute numbers of CD3+ T cells and CD8+ T cells during aging in herpes zoster patients.

Herpes zoster (HZ) is an infectious dermatosis with high incidence worldwide. Age is a key risk factor for HZ, and postherpetic neuralgia (PHN) is the main sequelae. Until now, no index has been available to predict the pathogenesis of PHN, and rare reports have focused on the immune response during aging and PHN. In this study, we selected immunoglobulin and complement proteins as markers for humoral immunity, while T lymphocyte subsets and natural killer (NK) cells were selected as markers for cell immunity, to systematically study the characteristics of immune responses in the peripheral blood of HZ patients. Our data showed that the absolute number of CD3+ T cells and CD8+ T cells decreased during aging and PHN. This implies that more attention should be paid to prevent the occurrence of PHN, especially in the aged population.