Identification of a novel fusion gene, TRIM52-RACK1, in oral squamous cell carcinoma.

Gene fusion is caused by the linkage of previously separate genes or sequences. Recently, an increasing number of novel fusion genes have been identified and associated with tumor progression, and several of them have been suggested as promising targets for tumor therapy. However, there are hardly any studies reporting the association of fusion genes with the progression of oral squamous cell carcinoma (OSCC). In this study, we identified a total of 11 fused genes in OSCC cells. We further analyzed the structure of one fused gene, TRIM52-RACK1, and detected its function in tumor progression in vitro. We found that TRIM52-RACK1 was caused by a deletion of 181,257,187-181,247,386 at 5q35.3 and it promoted OSCC cell proliferation, migration, and invasion. Therefore, TRIM52-RACK1 can be a promising target for tumor therapy in OSCC.

Integrated analysis of lncRNA CTD-2357A8.3 expression and its potential roles in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC), one of the most common malignant tumors, endangers human health. Recently, the incidence of HNSCC has kept increasing: However, its prognosis has not significantly improved. Understanding the molecular mechanism underlying HNSCC development will therefore provide new strategies for therapy. The present study attempted to identify differentially expressed (DE) long non-coding (lnc)RNAs and investigated their functional role in HNSCC development. Expression profiles of HNSCC and normal samples were downloaded from The Cancer Genome Atlas (TCGA) database. DElncRNAs between the HNSCC and normal samples were highlighted and their potential functions were investigated through lncRNA-micro (mi)RNA-mRNA network by using Gene Expression Profiling Interactive Analysis, UALCAN, DIANA-LncBase v.2 and miRWalk 3.0 databases. A total of 343 dysregulated lncRNAs were identified. Among these DElncRNAs, CTD-2357A8.3 had the highest fold-change and was significantly associated with poor overall survival in patients with HNSCC. Furthermore, CTD-2357A8.3 was associated with 'signaling pathways regulating stem cell pluripotency', 'proteoglycans in cancer', 'transcriptional misregulation in cancer' and 'chemokine signaling pathway'. Further analysis demonstrated that CTD-2357A8.3 acted as a 'sponge' in order to competitively adsorb miRNA to regulate the expression of target gene caveolin 1 (CAV1) in HNSCC. In conclusion, CTD-2357A8.3 may be considered a promising diagnosis biomarker or a therapeutic target for the treatment of HNSCC.

Integrin α-5 as a potential biomarker of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors that endanger human health. In recent years, the incidence of HNSCC has been increasing, without any significant improvement in the prognosis. Therefore, increased knowledge on the molecular mechanism underlying HNSCC development will allow the development of new strategies for therapy. The present study attempted to identify key genes involved in HNSCC development. Expression profiles of HNSCC and normal samples were downloaded from The Cancer Genome Atlas database. Differentially expressed genes (DEGs) between the HNSCC and normal samples were identified and subjected to Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis. A protein-protein interaction (PPI) network was constructed, and Cytoscape CentiScape and Gene Expression Profiling Interactive Analysis were used to identify key DEGs. Finally, expression profiles of HNSCCs, including 500 HNSCCs and 44 normal samples, were included in the analysis. A total of 1,181 DEGs were screened, among which 354 genes were upregulated and 827 genes were downregulated in HNSCC compared with normal tissues. The GO enrichment analysis showed that the DEGs were mainly involved in chloride transmembrane transporter, metalloendopeptidase and substrate-specific channel activities. The KEGG pathway analysis revealed that the DEGs were mainly associated with 'protein digestion and absorption', as well as 'extracellular matrix-receptor interaction'. Integrin α-5 (ITGA5) was identified as a hub gene, based on the PPI network complex, and was confirmed to be significantly associated with the overall survival rate. Moreover, ITGA5 was overexpressed specifically in HNSCC. The genes found, notably ITGA5, are potential diagnostic biomarkers and therapeutic targets in HNSCC.

Cancer­associated fibroblast­derived exosomal miR­382­5p promotes the migration and invasion of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC), with high potential for metastasis, is the most common malignant tumor of the head and neck. Cancer­associated fibroblasts (CAFs) are the main stromal cells in the microenvironment and aggravate tumor progression. However, whether CAFs are associated with the progression of OSCC remains unknown and the underlying mechanism remains unclear. In the present study, the role of CAFs in mediating OSCC cell migration and invasion was investigated, and the participation of exosomal miR­382­5p in this process was elucidated. In this study, according to the α­SMA staining with immunohistochemistry, 47 OSCC patients were divided into CAFs­rich and CAFs poor groups, and association of CAF density and clinicopathologic features of the OSCC patients were analyzed with Pearson χ2 test. Transwell assay was used for evaluating cell migration and invasion ability of OSCC cells after being co­cultured with NFs or CAFs, or after added exosomes. qPCR was used to detect the expression of miR­382­5p. Western blot analysis was used to measure the expression of migration and invasion­associated proteins. In the present study, the CAF density in tumor tissues was found to be relevant to OSCC lymph node metastasis and TNM stage. Furthermore, we revealed that miR­382­5p was overexpressed in CAFs compared with that in fibroblasts of adjacent normal tissue and miR­382­5p overexpression was responsible for OSCC cell migration and invasion. Finally, we demonstrated that CAF­derived exosomes transported miR­382­5p to OSCC cells. The present study confirmed a new mechanism of CAF­facilitated OSCC progression and may be beneficial for identifying new cancer therapeutic targets.

Prognostic value of long non-coding RNA plasmacytoma variant translocation1 in human solid tumors: A meta-analysis.

Plasmacytoma variant translocation 1 (PVT1) is highly expressed in a variety of cancer tissues and is related to the clinicopathological features and prognosis. However, the prognostic value of PVT1 is still controversial. Therefore, this systematic evaluation and meta-analysis were performed to evaluate the relationship between PVT1 expression and clinicopathological features.PubMed, EMBASE, Web of science, and Cochrane library databases were searched for literature collection according to inclusion criteria and exclusion criteria. The pooled hazard ratios (HRs) or odds ratios (ORs) were used to evaluate the association between PVT1 expression and overall survival, tumor size, tumor-node-metastasis (TNM) stage, lymph node metastasis, and distant metastasis.A total of 39 articles including 3974 patients were included in the study. The results showed that the expression of PVT1 was closely related to the overall survival rate of cancers (HR = 1.64, 95% confidence interval [CI]: 1.50-1.78, P < .000001). Subgroup analysis showed that the high expression of PVT1 was closely related to the low overall survival rate of patients with clear cell renal cell carcinoma, breast cancer, cervical cancer, colon cancer, epithelial ovarian cancer, gastric cancer, lung cancer, and osteosarcoma. In addition, the high expression of PVT1 was positively correlated with tumor size (OR = 1.50, 95% CI: 1.14-1.96, P = .004), TNM stage (OR = 3.39, 95% CI: 2.73-4.20, P < .00001), lymph node metastasis (OR = 2.60, 95% CI: 1.76-3.84, P < .00001), and distant metastasis (OR = 2.94, 95% CI: 1.90-4.56, P < .00001).PVT1 could serve as a marker for the size, TNM stage, metastasis, and prognosis of different type of cancers.

Identification of key candidate genes and pathways in oral squamous cell carcinoma by integrated Bioinformatics analysis.

Oral squamous cell carcinoma (OSCC) is one of the most common types of malignant head and neck tumor, which poses a serious threat to human health. In recent years, the incidence of OSCC has been increasing, while the prognosis has not significantly improved. Elucidation of the molecular mechanisms underlying the development of OSCC may provide novel therapeutic strategies. In the present study, the gene expression profiles from 4 datasets, including 244 OSCC and 95 normal oral mucosa samples, were subjected to statistical and Bioinformatics analysis. A total of 34 differentially expressed genes (DEGs) were identified, among which 14 were upregulated and 20 were downregulated in OSCC compared with normal oral mucosa tissues. Gene Ontology enrichment analysis indicated that the DEGs were mainly involved in regulation of the immune response, cell adhesion and cell proliferative processes. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were mainly associated with the phosphoinositide-3 kinase Akt and Toll-like receptor signaling pathway. The key candidate DEGs were identified from the complex protein-protein interaction network, and secreted phosphoprotein 1 (SPP1), integrin subunit α 3 and plasminogen activator, urokinase (PLAU) were confirmed to be significantly associated with the survival rate. Cell Counting Kit-8 and Transwell assays demonstrated that SPP1 and PLAU regulate cell proliferation, migration and invasion. The candidate genes/pathways identified in the present study may include promising diagnostic biomarkers or therapeutic targets for OSCC.

The efficacy of polidocanol sclerotherapy in mucocele of the minor salivary gland.

OBJECTIVES: Mucocele of the minor salivary gland is usually caused when the duct is injured, mucus leaks into the tissue space and the mucous gland are obstructed, which lead to cystic lesion formation and dilatation. Currently, there are multiple therapeutic methods available with various outcomes. This study aims to provide clinical evidence of polidocanol sclerotherapy for the treatment of mucocele of the minor salivary gland. METHODS: In this study, we injected polidocanol into 112 patients who were diagnosed with mucocele of the minor salivary gland and evaluated the treatment efficacy and safety systematically. RESULTS: Of the 122 cases, 102 cases were cured, eight cases showed remarkable remission, and two cases had partial remission. No recurrence was found during follow-up, and none of the cases showed an invalid effect, resulting in a total cure rate of 91.07%. No severe side effects were observed during treatment or the follow-up period. No significant difference in efficacy between different genders was found (P = 0.490). Polidocanol sclerotherapy for mucocele on the lower lip was more effective compared to mucocele on the inferior surface of the lingual apex (P = 0.035). CONCLUSION: Polidocanol sclerotherapy showed satisfying curative effects for mucocele of the minor salivary gland without causing side effects of anesthesia, trauma, or severe pain.

[Clinicopathological and prognostic significance of PD-L1 expression in oral squamous cell carcinoma: a meta analysis].

PURPOSE: To determine the prognostic role of high PD-L1 in patients with oral squamous cell carcinoma. METHODS: Electronic databases, such as PubMed, Embase and Cochrane library, were searched to identify studies evaluating PD-L1 expression and overall survival (OS) in these patients. RevMan 5.3 software was used for meta-analysis. RESULTS: A total of 12 studies that involved 1595 patients were included. Pooled hazard ratio (HR) 1.02 (95%CI= 0.93-1.11,P=0.71) indicated that the association between PD-L1 expression and overall survival (OS) was not significant. The pooled odds ratios (ORs) indicated that PD-L1 expression was associated with gender (OR=0.64, 95%CI=0.48-0.85, P=0.002), differentiation (OR=0.58, 95%CI=0.37-0.90, P=0.01) and HPV infection (OR=1.91, 95%CI=1.13-3.23, P=0.02). However, PD-L1 had no correlation with tumour size, and lymph node status. CONCLUSIONS: PD-L1 expression may not be an independent predictor of prognosis of patients with OSCC. Well-designed large cohort studies are needed to confirm these findings.

Betulinic acid increases radiosensitization of oral squamous cell carcinoma through inducing Sp1 sumoylation and PTEN expression.

Radiotherapy is one of the most effective non-surgical treatments for oral squamous cell carcinoma. However, radioresistance remains a major impediment to radiotherapy. Although BetA (Betulinic acid) can induce radiosensitization, the underlying mechanism and whether it could induce radiosensitization in oral squamous cell carcinoma are not fully understood. In this study, we showed that BetA increased radiosensitization in CAL-27 and Tca-83 cells. Radiation-triggered Sp1 overexpression was responsible for radioresistance of OSCC (oral squamous cell carcinoma) cells. Treatment with BetA downregulated Sp1 and upregulated PTEN through inducing Sp1 sumoylation and correspondingly increased radiosensitization. Moreover, Sumoylation of Sp1 upregulated PTEN protein expression by downregulating Sp1 as well as inhibiting Sp1 DNA binding activity, thereby leading to the activation of PTEN transcription. Our results suggested that BetA was able to enhance radiosensitization at least partially by downregulating Sp1 and upregulating PTEN through inducing Sp1 sumoylation. BetA is suggested to be a promising drug for increasing radiosensitization in oral squamous cell carcinoma radiotherapy.

Inhibition of autophagy augments apoptosis in human oral squamous cell carcinoma under nutrient depletion.

There has been little research conducted regarding autophagy in oral squamous cell carcinoma (OSCC). Given the prevalence of oral cancers which are OSCC and the severe side effects of current treatments, there is a pressing need to develop effective alternative therapies. In this study, we have endeavored to explore the biological characteristics of oral squamous cell carcinoma cell line KB cells, in particular with regard to the role played by autophagy in their survival. Autophagy was activated by nutrient depletion via culturing cells in Earle's balanced salts (EBSS) and was measured via indices relating to Beclin 1, microtubule-associated protein light chain 3 (MAPLC3, LC3), p62, and Green fluorescent protein-light chain 3 plasmid transfection (GFP-LC3). Cell death and apoptosis induced by nutrient depletion was measured using both MTT assay and flow cytometry (FCM). Compared to initial levels at 0 h, Beclin 1 density in EBSS-treated cells was found to have increased at 6, 12, and 18 h in a time-dependent manner and was found to have subsequently declined at 24 and 48 h. p62 levels, LC3-II/LC3-I ratio, and GFP-LC3 levels increased at 6, 12, 18, 24, and 48 h in a time-dependent manner. 3-methyladenine (3-MA) was found to inhibit autophagy and the expression of Beclin 1 and significantly enhanced nutrient depletion-induced apoptosis and death. We concluded that nutrient depletion enhances OSCC cell autophagy in time-course patterns and that the inhibition of autophagy augments apoptosis in OSCC cells. We also deduced that Beclin 1 takes part in the development and progression of autophagy, potentially playing an important role in the crosstalk between apoptosis and autophagy in OSCC cells. These findings suggest that nutrient depletion may be an effective way to explore autophagy and that autophagy inhibitors should be investigated as a potential novel agent for the adjuvant treatment of human OSCC.

Lentivirus-based RNA silencing of Nemo-like kinase (NLK) inhibits the CAL 27 human adenosquamos carcinoma cells proliferation and blocks G0/G1 phase to S phase.

BACKGROUND: The Nemo-like kinase (NLK) is a serine/threonine-protein kinase that involved in a number of signaling pathways regulating cell fate. Variation of NLK has been shown to be associated with the risk of cancer. However, the function of NLK in oral adenosquamous carcinoma cells line CAL-27 is unknown. METHODS: In this study, we evaluated the function of NLK in CAL-27 cells by using lentivirus-mediated RNA silence. The targeted gene expression, cell proliferation and cell cycle are investigated by RT-PCR, western-blot, MTT method, colony forming assay and flow cytometry analysis respectively. RESULTS: After NLK silencing, the number of colonies was significantly reduced (54 ± 5 colonies/well compared with 262 ± 18 colonies/well in non-infected or 226 ± 4 colonies/well in negative control group (sequence not related to NLK sequence with mismatched bases). Using crystal violet staining, we also found that the cell number per colony was dramatically reduced. The RNA silencing of NLK blocks the G0/G1 phase to S phase progression during the cell cycle. CONCLUSIONS: These results suggest that NLK silencing by lentivirus-mediated RNA interference would be a potential therapeutic method to control oral squamous carcinoma growth.