TGF-ßRII/EP300/SMAD4 cascade signaling pathway promotes invasion and glycolysis in oral squamous cell carcinoma.

INTRODUCTION: EP300 is considered to be a cancer suppressor gene that plays a role in tumor development, but some studies have reported that it is not an oral squamous cell carcinoma suppressor gene, because there was neither epigenetic inactivation of the gene nor a mutation resulting in functional impairment. However, there is no relevant study on whether EP300 is the exact carcinogenic effect and its mechanisms of carcinogenic effects in oral squamous cell carcinoma. METHODS: Western blot analysis and quantitative real time polymerase chain reaction experiments verified the protein and mRNA expression of EP300 in oral squamous cell carcinoma; The effects of EP300 knockout on glucose consumption and lactic acid production were detected by glycolysis experiments; The relationship between pathway-related proteins and EP300 was verified by bioinformatics analysis and co-immunoprecipitation experiment. RESULTS: Our experimental results confirm that the protein and mRNA of EP300 are highly expressed in oral squamous cell carcinoma, and after knocking out the EP300, the glycolysis ability, invasion, migration, and other biological functions of oral squamous cell carcinoma, are inhibited at the same time. Pathway-related experiments have confirmed that EP300 plays a role in promoting cancer through the transforming growth factor-beta receptor II (TGF-ßRII)/EP300/Smad4 cascade pathway. CONCLUSION: EP300 plays a carcinogenic role in OSCC showed that the TGF-ßRII/EP300/Smad4 cascade pathway is involved in oral squamous cell carcinoma.

TRAP1 suppresses oral squamous cell carcinoma progression by reducing oxidative phosphorylation metabolism of Cancer-associated fibroblasts.

BACKGROUND: Glucose metabolism in cancer associated fibroblasts (CAFs) within the tumor microenvironment is a material and energy source for tumorigenesis and tumor development. However, the characteristics and important regulatory mechanisms of glucose metabolism in fibroblasts associated with oral squamous cell carcinoma (OSCC) are still unknown. METHODS: We successfully isolated, cultured, purified and identified CAFs and normal fibroblasts (NFs). Cell culture, immunohistochemistry (IHC) and CCK8, flow cytometry, Seahorse XF Analyzer, MitoTracker assay, western blotting (WB), transmission electron microscope, Quantitative real-time PCR (qPCR), immunofluorescence (IF), and Label-free quantitative proteomics assay, animal xenograft model studies and statistical analysis were applied in this study. RESULTS: We demonstrated that the proliferation activity of CAFs was significantly enhanced as compared to NFs, while the apoptosis rate was significantly decreased. CAFs in OSCC preferentially use oxidative phosphorylation (OXPHOS) rather than glycolysis. Moreover, CAFs showed stronger maximal respiration, a larger substantial mitochondrial spare respiratory capacity (SRC) and higher adenosine triphosphate (ATP) production capacity than NFs. The results of mitotracker green fluorescence staining showed that compared with NFs, CAFs exhibited stronger green fluorescence. The results of WB showed the expression level of Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) obviously increased in CAFs compared to NFs. These results confirmed that CAFs have greater mitochondrial activity and function than NFs. Furthermore, Label-free quantitative proteomics assays showed that both ATP synthase subunit O (ATP5O) and tumor necrosis factor receptor-associated protein 1 (TRAP1) are important differentially expressed proteins in the mitochondria of CAFs/NFs. Overexpression of TRAP1 in CAFs increased basal oxygen consumption rate (OCR), maximal respiration, ATP production and SRC. In vivo, overexpression TRAP1 expression in CAFs suppress tumor growth. CONCLUSION: Taken together, the results indicated that TRAP1 is an important regulatory molecule of CAFs glucose metabolism and promotes OSCC progression by regulating the OXPHOS of CAFs.

Junction plakoglobin, a potential prognostic marker of oral squamous cell carcinoma, promotes proliferation, migration and invasion.

BACKGROUND: Junction plakoglobin (JUP) is an important cell-cell junction protein. Recently, its deregulation has been correlated with the initiation and progression of various malignancies. Our aim was to investigate the expression of JUP in oral squamous cell carcinoma (OSCC) and its correlation with prognosis and to further study the effects of JUP on the proliferation, apoptosis, migration and invasion of OSCC cells. METHODS: We detected JUP expression in 273 OSCC specimens using immunohistochemistry. We assessed the correlation of JUP expression with clinicopathologic parameters and patient survival by Cox regression. Then, expression levels of JUP in normal oral keratinocytes (NOKs) and OSCC cell lines were detected by Western blotting and quantitative real-time PCR (qPCR). Next, we used HSC3 cells to study the effect of JUP on tumor cell proliferation, apoptosis, migration, and invasion by using cell counting kit-8, flow cytometry, and transwell assays, respectively. RESULTS: Cox regression showed that high expression of JUP was related to the poor prognosis of OSCC patients. Western blotting and qPCR assays showed that the expression level of JUP in OSCC cell lines was higher than that in NOKs. Overexpression of JUP promoted the proliferation, metastasis, and invasion of HSC3 cells and inhibited apoptosis, while the opposite was observed after JUP knockdown. CONCLUSION: This study initially revealed that JUP was overexpressed in OSCC, and that JUP promoted the proliferation, migration, and invasion of OSCC cells and inhibited apoptosis. Moreover, high expression of JUP could be used as a potential prognostic marker of OSCC.

Retrospective summary analysis on the results of oral health epidemiological investigations in China.

Objective: Comparative analysis of the results of the four national oral health epidemiological investigations conducted in 1983, 1995, 2005 and 2015 respectively, to understand the changes in the oral health status of the Chinese people with economic development, and provide a scientific basis for the country to formulate effective oral health defense measures. Methods: Collect the data of four large-scale oral health epidemiological investigations conducted in the past 40 years, make a retrospective summary and comparative analysis of the list below to understand the changes in Chinese oral health-related indicators such as dental caries and analyze the reason. Results: Since 1995, the preventive counseling rate was increased. Since 1983, the incidence of caries has decreased, but it has increased in children aged 5 and 12 in the last ten years. Four investigations have examined gingivitis and the situation has not improved significantly. Tooth loss was mainly concentrated in the old group, the repair rate of denture was significantly increased. There are significant differences between the gender and urban and rural distribution of oral health. Conclusions: There is an imbalance in the degree of oral health knowledge of Chinese people, and the incidence of caries and periodontal diseases is still relatively high. It is necessary to strengthen hygiene guidance for different age groups, focusing on prevention and combining prevention and treatment to jointly promote oral health.

The effect of periodontal bacteria infection on incidence and prognosis of cancer: A systematic review and meta-analysis.

BACKGROUND: Periodontal bacteria is the major pathogens in the oral cavity and the main cause of adult chronic periodontitis, but their association with incidence and prognosis in cancer is controversial. The aim of this study was to evaluate the effect of periodontal bacteria infection on incidence and prognosis of cancer. METHODS: A systematic literature search of PubMed, Embase, Web of Science, and Cochrane Library databases was performed to obtain 39 studies comprising 7184 participants. The incidence of cancer was evaluated as odd ratios (OR) with a 95% confidence interval (95% CI) using Review Manager 5.2 software. Overall survival, cancer-specific survival and disease-free survival, which were measured as hazard ratios (HR) with a 95% CI using Review Manager 5.2 software. RESULTS: Our results indicated that periodontal bacteria infection increased the incidence of cancer (OR = 1.25; 95%CI: 1.03-1.52) and was associated with poor overall survival (HR = 1.75; 95% CI: 1.40-2.20), disease-free survival (HR = 2.18; 95%CI: 1.24-3.84) and cancer-specific survival (HR = 1.85, 95%CI: 1.44-2.39). Subgroup analysis indicted that the risk of cancer was associated with Porphyromonas gingivalis (Pg) infection (OR = 2.16; 95%CI: 1.34-3.47) and Prevotella intermedia (Pi) infection (OR = 1.28; 95%CI: 1.01-1.63) but not Tannerella forsythia (Tf) (OR = 1.06; 95%CI: 0.8-1.41), Treponema denticola (Td) (OR = 1.30; 95%CI: 0.99-1.72), Aggregatibacter actinomycetemcomitans (Aa) (OR = 1.00; 95%CI: 0.48-2.08) and Fusobacterium nucleatum (Fn) (OR = 0.61; 95%CI: 0.32-1.16). CONCLUSION: This meta-analysis revealed periodontal bacteria infection increased the incidence of cancer and predicted poor prognosis of cancer.