Propionate-producing Veillonella parvula regulates the malignant properties of tumor cells of OSCC.

Oral squamous cell carcinoma (OSCC), main head and neck squamous cell carcinomas (HNSCCs), remains a global health concern with unknown pathogenesis. Veillonella parvula NCTC11810 was observed to decrease in saliva microbiome of OSCC patients in this study and the aim was to detect the novel role of Veillonella parvula NCTC11810 in regulating the biological characteristics of OSCC through TROP2/PI3K/Akt pathway. Oral microbial community changes of OSCC patients were detected by 16S rDNA gene sequencing technology. CCK8 assay, Transwell assay, and Annexin V-FITC/PI staining were used for proliferation, invasion, and apoptosis analysis of OSCC cell lines. Expression of proteins were determined by Western blotting analysis. Veillonella parvula NCTC11810 showed decreased in saliva microbiome of TROP2 high-expressed OSCC patients. Culture supernatant of Veillonella parvula NCTC11810 promoted the apoptosis and inhibited the proliferation and invasion ability of HN6 cells, while sodium propionate (SP), the main metabolite of Veillonella parvula NCTC11810, played a similar role through the inhibition of TROP2/PI3K/Akt pathway. Studies above supported the proliferation-inhibiting, invasion-inhibiting, and apoptosis-promoting function of Veillonella parvula NCTC11810 in OSCC cells which provided new insights into oral microbiota and their metabolite as a therapeutic method for OSCC patients with TROP2 high expressing.

Oncostatin M receptor is overexpressed in oral squamous cell carcinoma and connected to poor prognosis.

BACKGROUND: Oncostatin M receptor is an interleukin 6 receptor with great influence on inflammation and cancer progression. However, the function of oncostatin M receptor in oral squamous cell carcinoma remains unknown. METHODS: Oncostatin M receptor expression was explored with TIMER and TCGA databases. The mRNA and protein expressions of oncostatin M receptor were detected in oral tissues. The association between oncostatin M receptor expression and clinicopathological characteristics was analyzed, and the prognostic value of oncostatin M receptor was determined. Immune statues of oncostatin M receptor were analyzed by TIMER and TISIDB. The underlying mechanisms of oncostatin M receptor in oral squamous cell carcinoma was also explored preliminarily. RESULTS: Oncostatin M receptor was dysregulated in many cancers. Both mRNA and protein levels of oncostatin M receptor in oral squamous cell carcinoma tissues were significantly higher than that in normal oral tissues. Oncostatin M receptor expression was connected to differentiation, lymph node metastasis, tumor node metastasis (TNM) stage, perineural invasion and vascular invasion. Oncostatin M receptor expression was an independent prognostic factor associated with overall survivals. Oncostatin M receptor expression was significantly related to CD8+ T cell and interleukin 6 receptor. High oncostatin M receptor expression was associated with focal adhesion, extracellular matrix (ECM) receptor interaction, and JAK/STAT signaling pathway. CONCLUSION: Oncostatin M receptor was overexpressed in oral squamous cell carcinoma and related to overall survival. Oncostatin M receptor expression has potential to become an effective prognostic biomarker for oral squamous cell carcinoma patients.

[Analysis of clinical phenotype and genetic variant in a Chinese pedigree affected with cleidocranial dysplasia].

OBJECTIVE: To analyze the clinical features and pathogenic variant in a Chinese pedigree affected with cleidocranial dysplasia (CCD). METHODS: Clinical data of 8 patients from the pedigree was collected, including physical examination and X-ray images of head, face, spine, limbs, and mouth. Peripheral blood samples were collected from 6 affected members for the extraction of genomic DNA. The proband and other 3 patients were subjected to trio-whole exome sequencing. Candidate variant was verified by Sanger sequencing of the other 2 affected members from the pedigree. RESULTS: This pedigree has included 22 members (8 affected) from four generations. Genetic testing revealed that the proband has harbored a novel pathogenic variant of the RUNX2 gene [NM_001024630: c.1268_1277del (p.P425Afs*56)], which was inherited from her mother and carried by all affected members in the pedigree. The same variant was not detected among the unaffected members, suggesting co-segregation with the phenotype. CONCLUSION: The c.1268_1277del (p.P425Afs*56) variant of the RUNX2 gene probably underlay the pathogenesis of CCD in this pedigree. Genetic testing has facilitated the definite diagnosis and enabled prenatal diagnosis.

Pyrroloquinoline quinone inhibits ligature-induced alveolar bone loss through regulation of redox balance and cell senescence.

It has been demonstrated that oxidative stress is related to periodontitis, and that pyrroloquinoline quinine (PQQ) acts as a powerful antioxidant. This study aimed to explore the effect of PQQ on ligature-induced alveolar bone loss in experimental periodontitis (EP) mice with/without PQQ in the diet. EP mice received a diet supplemented with PQQ for 2 weeks and were compared with sham (control) mice as well as untreated EP mice. Additionally, human periodontal ligament cells (hPDLCs) were treated with PQQ in the presence or absence of lipopolysaccharide (LPS). We found that the bone volume fraction, alkaline phosphatase activity, and the number of antioxidant cells were significantly decreased in EP mice compared with the sham mice, whereas PQQ administration rescued the above effects. In contrast, alveolar bone loss, osteoclast number, cell senescence-associated cells, and cytokines' expression were significantly increased in EP mice compared with the sham mice but were significantly decreased with PQQ supplementation in periodontal tissues. Furthermore, we found that antioxidant enzymes and Bmi-1 protein expression levels were downregulated, whereas the protein expression levels of cell senescence-related proteins including γ-H2AX, IL-6, IL-1ß, p16, and p21 were significantly up-regulated in LPS-induced hPDLCs compared with the control cells. However, PQQ administration partially prevented these changes. These findings suggest that PQQ may alleviate periodontal damage through regulation of the redox balance and cell senescence.

POM121 is a novel marker for predicting the prognosis of laryngeal cancer.

The nuclear pore membrane protein 121 (POM121) is an important member of the nuclear pore complex which regulates nucleocytoplasmic transport, but little is known about the role of POM121 in laryngeal cancer. In this study, quantitative real-time polymerase chain reaction and immunohistochemistry were performed to detect POM121 expression in laryngeal tissues. The associations between POM121 and clinicopathological characteristics and overall survival in laryngocarcinoma patients were also analyzed. The mechanism of POM121 was preliminarily explored through gene set enrichment analysis (GSEA). mRNA and protein expression of POM121 in laryngocarcinoma tissues were higher than those in nontumor tissues. High POM121 expression was positively correlated with poor differentiation (χ²=42.391, P<0.001), advanced distant metastases (χ²=20.346, P<0.001) and TNM stage (χ²=23.436, P<0.001). Laryngocarcinoma patients with high POM121 level tended to have poor overall survival. GSEA confirmed that the mechanism of POM121 in laryngeal cancer may relate to sphingolipid metabolism, lysosome, fatty acid metabolism, ribosome, nucleotide excision repair and the PPAR signaling pathway. Overall, POM121 expression might be a prognostic biomarker in laryngeal cancer, and POM121 has the potential to present as a therapeutic target for laryngocarcinoma patients.

Overexpression of PSMA7 predicts poor prognosis in patients with gastric cancer.

Gastric cancer (GC) is the fourth most common tumor and the second most common cause of cancer-associated mortality worldwide. Current tumor biomarkers for GC, such as serum carcinoembryonic antigen and carbohydrate antigen 19-9, are not ideal due to their limited role as prognostic indicators for GC. Proteasome subunit α7 (PSMA7) is a multifunctional protein, which has been revealed to be involved in the development and progression of various types of malignancy. However, little is known about the role of PSMA7 in GC. In the present study, PSMA7 was identified to be overexpressed at the mRNA and protein levels in GC tissues, compared with in non-tumor tissues, using reverse transcription-quantitative PCR and immunohistochemistry. Furthermore, PSMA7 expression is associated with tumor invasion, lymph node metastasis, distant metastasis, and Tumor-Node-Metastasis stage. Univariate and multivariate Cox regression analysis identified that PSMA7 expression is an independent prognostic factor for poor survival. Kaplan-Meier survival curves revealed that high PSMA7 expression is associated with a poor prognosis in patients with GC. Overall, the results of the present study suggested that PSMA7 may be a promising biomarker for the prognosis of GC, and may represent a new diagnostic marker and molecular therapeutic target for GC.

TROP2 increases growth and metastasis of human oral squamous cell carcinoma through activation of the PI3K/Akt signaling pathway.

Most malignant neoplasms of the oral cavity are oral squamous cell carcinoma (OSCC), which is a type of highly malignant tumor with a propensity for forming distant metastases. Trophoblast cell surface antigen 2 (TROP2) is a transmembrane protein that is overexpressed in several types of tumor cells, although its role and regulatory mechanism in OSCC have not been determined. The aim of the present study was to examine the effects of TROP2 in human OSCC cell lines. The present study demonstrated that TROP2 protein expression was upregulated in OSCC cell lines. Transfection of short hairpin RNA (shRNA) targeting TROP2 (sh­TROP2) reduced cell proliferation, migration and invasion of OSCC cell lines, whereas overexpression of TROP2 increased proliferation, migration and invasion. sh­TROP2 transfection in OSCC cell lines inhibited tumor growth in OSCC mouse models. Furthermore, TROP2 expression activated the phosphoinositide 3­kinase (PI3K)/Akt signaling pathway in human OSCC cells. These results suggest that TROP2 induces cell growth, migration and invasion through activation of the PI3K/Akt signaling pathway in OSCC cells.

POM121 is identified as a novel prognostic marker of oral squamous cell carcinoma.

Background: The aim of this study was to confirm the role of nuclear pore membrane protein 121(POM121) in oral squamous cell carcinoma and to explore the underlying mechanism. Methods: POM121mRNA and protein expressions were evaluated in OSCC tissues and normal oral tissues by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. The relationship between POM121 expression and clinical characteristics was analyzed. Bioinformatics analysis was performed to explore the possible mechanisms how POM121 affected OSCC. Results: We confirmed that POM121 mRNA expression in OSCC tissues was significantly higher than that in non-tumorous tissues, as was POM121 protein expression. POM121 expression was associated with distant metastasis and TNM stage. Multivariate analysis confirmed POM121 expression as an independent prognostic factor for OSCC patients. OSCC patients with high POM121 expression had a worse overall survival (OS) compared with patients with low POM121 expression. Bioinformatics analysis indicated POM121 may regulate OSCC through hedgehog and /or p53 signaling pathway. Conclusion: Targeting of POM121 expression levels could provide new diagnostic and therapeutic strategies for OSCC patients.

High expression of TROP2 is correlated with poor prognosis of oral squamous cell carcinoma.

Human trophoblastic cell-surface antigen 2 (TROP2) is a cell surface glycoprotein that exhibits high expression in various carcinomas but low or no expression in normal tissues. High TROP2 expression plays an important role in promoting tumor development and aggressiveness, which is correlated with reduced patient survival. However, there are few studies regarding TROP2 in relation to both oral squamous cell carcinoma (OSCC) and oral potentially malignant lesions. The expression of TROP2 protein and mRNA was investigated in OSCC tissues, oral potentially malignant lesion tissues, and normal oral tissues using immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). The association between TROP2 expression and clinicopathological characteristics of OSCC was also analyzed, and the prognostic value of TROP2 was evaluated. The expression of TROP2 protein and mRNA were both higher in OSCC tissues than in oral potentially malignant lesion tissues or normal oral tissues. Positive TROP2 expression was related to differentiation, lymph node metastases, TNM stage, perineural infiltration, and vascular invasion. Poor overall survival was associated with high TROP2 expression and other factors associated with poor overall survival including poor differentiation, lymph node metastasis, TNM stage, vascular invasion, and perineural invasion in univariate analyses. TROP2 expression as well as TNM stage and vascular invasion were independent prognostic factors associated with the overall survival of OSCC patients in multivariate analyses. In summary, High TROP2 expression is associated with poor overall survival and serves as an independent prognostic factor in OSCC. The results suggest that TROP2 expression could be an effective prognostic biomarker for OSCC.