Tongue Squamous Cell Carcinoma Tissues Research Articles

Suppression of KIF22 Inhibits Cell Proliferation and Xenograft Tumor Growth in Tongue Squamous Cell Carcinoma.

Background Oral carcinoma is the sixth most common cancer and is a serious public health problem, and tongue squamous cell carcinoma (TSCC) is the most common type of oral carcinoma. Kinesin family member 22 (KIF22), also called as kinesin-like DNA binding protein (KID), is a microtubule-based motor protein and binds to both microtubules and chromosomes, transporting organelles, protein, and mRNA. This research aimed at investigating the prognostic significance of KIF22 in TSCC. Patients and Methods. This retrospective research collected 82 paired tissues with TSCC. KIF22 protein expression level was detected by immunohistochemical staining. Suppression of KIF22 with shRNA in CAL-27 and SCC-15 cells was to observe cell proliferation in vitro and xenograft tumor growth in vivo. Results In TSCC tissues, the protein expression level of KIF22 was increased and correlated with tumor stage, clinical stage, and lymphatic metastasis (P=0.013, P=0.013, P=0.013, Conclusion KIF22 might play an important role in the progression of TSCC and could serve as a therapeutic target for TSCC.

Long non-coding RNA LINC00152 acts as a sponge of miRNA-193b-3p to promote tongue squamous cell carcinoma progression.

Dysregulated expression of long non-coding RNAs has been determined to be important in cancer development; however, their role in tongue squamous cell carcinoma (TSCC) progression and carcinogenesis, to the best of our knowledge, is yet to be elucidated. The present study revealed that long intergenic non-coding RNA 00152 (LINC00152) expression was significantly increased in human TSCC tissues compared with in tissues from matched controls using RT-qPCR. In TSCC cell lines, CAL-27 and SCC-9, LINC00152 was revealed to promote TSCC cell proliferation, enhance cell cycle progression and inhibit cell apoptosis. Additionally, migration and invasion of TSCC cell lines was increased in response to LINC00152 overexpression. Mechanistically, LINC00152 was determined to be localized in the cytoplasm and acted as a microRNA (miR)-193b-3p sponge, and LINC00152 knockdown or miR-193b-3p mimics both inhibited PI3K signaling pathway activation and downstream AKT phosphorylation; therefore, promoting TSCC progression in vitro. Overall, the results of the present study suggested that increased LINC00152 expression in TSCC tissues may act as a sponge of miR-193b-3p to promote cancer progression in vitro.

<p>LncRNA CASC9 Affects Cell Proliferation, Migration, and Invasion of Tongue Squamous cell Carcinoma via Regulating miR-423-5p/SOX12 Axes</p>

IntroductionThe incidence of tongue squamous cell carcinoma (TSCC) has increased in recent decades. However, the function of long non-coding RNA (lncRNA) CASC9 in the occurrence and progression of TSCC is unclear. In this work, we attempted to clarify the role of lncRNA CASC9 in determining the phenotype of TSCC cells, and to clarify the underlying mechanisms.MethodsWe used qRT-PCR analysis to identify the level of CASC9 mRNA expression in TSCC clinical samples and cell lines. We investigated cell proliferation, and cell migration and invasion of TSCC cells transfected with siCASC9 or siNC using CCK-8 and transwell assays. Bioinformatics analysis and a luciferase reporter assay were employed to predict and verify the target microRNA (miRNA).ResultsCASC9 was up-regulated in the TSCC tissues and cells, and predicted a poor prognosis. CASC9 silencing significantly inhibited cell proliferation, migration, and invasion of the TSCC cells compared with the non-targeting control small interfering RNA (siCtrl) treatment. miR-423-5p was predicted as the targeting miRNA of CASC9; this was verified by a luciferase reporter assay. CASC9 expression showed a negative correlation with miR-423-5p expression and a positive correlation with SOX12 expression. The miR-423-5p inhibitor can rescue the carcinogenesis effect of CASC9 on TSCC cells.ConclusionOur work indicates that CASC9 plays a role in TSCC tumorigenesis; this novel information will improve TSCC molecular targeting therapy.

Diverse Region-Based CNN for Tongue Squamous Cell Carcinoma Classification With Raman Spectroscopy

Border discrimination is very important in the treatment of tongue squamous cell carcinoma (TSCC). This study proposes an ensemble convolutional neural network (CNN) framework based on fiber optic Raman spectroscopy and deep learning techniques to distinguish between TSCC and non-tumor tissue frameworks. First, the data used in the experiments was collected by a fiber optic Raman system. A total of 44 tissues of 22 patients were collected for Raman spectroscopy, with TSCC and adjacent normal tissues each accounting for half. The spectral data range used in the model from a full spectrum of 600-4000 cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> . Then, the ensemble CNN model was used in the experiment. By using two convolution kernels, the model is able to extract nonlinear feature representations from different spectral regions. It has two advantages, on the one hand, it reduces the generation of noise, on the other hand, it obtains a stronger distinguishing ability. Finally, a feature vector is formed by the fusion layer, and is sent to the fully connected layer for the TSCC classification task. The results showed that the sensitivity and specificity of the model were 99.2% and 99.2%, respectively. In addition, comparison with existing methods shows that our method achieves the highest accuracy of TSCC classification. By comparing the different channels, the results show that the spectral range of 1380-2250cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-1</sup> data has the greatest impact on the results. Therefore, Raman spectroscopy combined with the ensemble CNN model has great potential and can provide a useful technique for intraoperative evaluation of the margins of oral tongue squamous cell carcinoma.

MTHFD1L-Mediated Redox Homeostasis Promotes Tumor Progression in Tongue Squamous Cell Carcinoma.

Background: Routine changes in cell metabolism can drive tumor development, as the cellular program develops to promote glycolysis and redox homeostasis during tumor progression; however, the associated mechanisms in tongue squamous cell carcinoma (TSCC) remain unclear.Methods: We investigated methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) expression, its clinical relevance, redox modification, and molecular mechanisms using TSCC cells and tissues. The anti-tumor effects of MTHFD1L knockdown on TSCC tumorigenesis were evaluated in vitro and in vivo. Kaplan-Meier curves and the log-rank test were used to analyze disease-free survival and overall survival.Results: TSCC patients with high expression levels of MTHFD1L had shorter overall survival (P < 0.05) and disease-free survival (P < 0.05). Knockdown of MTHFD1L reduced nicotinamide adenine dinucleotide phosphate (NADPH) levels and increased reactive oxygen species (ROS), which accelerated cell death under oxidative stress, such as hypoxia or glucose deprivation. Additionally, inhibition of MTHFD1L suppressed TSCC cell growth and delayed the cell cycle, including in xenograft experiments.Conclusions: MTHFD1L confers redox homeostasis and promotes TSCC cell growth, which provides a great opportunity to study tumor metabolism in head and neck cancer. The mTORC1-4EBP1-eIF4E axis may affect the expression of MTHFD1L in TSCC. Inhibition of the expression of MTHFD1L may be an actionable and effective therapeutic target in TSCC.

Circ_0001742 promotes tongue squamous cell carcinoma progression via miR-431-5p/ATF3 axis.

Circular RNAs (circRNAs) have been demonstrated to involve in the development of various cancers. This study aimed to investigate the functions of circ_0001742 on regulating tongue squamous cell carcinoma (TSCC) development and the underlying mechanisms. The expression of circ_0001742, miR-431-5p and activating transcription factor 3 (ATF3) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of epithelial-mesenchymal transition (EMT)-related proteins and ATF3 were measured by Western blot analysis. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry assay were used to evaluate cell proliferation and apoptosis. Besides, Cell migration and invasion were assessed by transwell assay. The relationships between circ_0001742 and miR-431-5p, miR-431-5p and ATF3 were predicted by online software and confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and pull-down assay. The expression of circ_0001742 was upregulated in TSCC tissues and cells. Knockdown of circ_0001742 inhibited proliferation, migration, invasion and EMT and induced apoptosis in TSCC cells. Then, miR-431-5p was identified as a target of circ_0001742, and knockdown of miR-431-5p reversed the effects of circ_0001742 knockdown on proliferation, apoptosis, migration, invasion and EMT of TSCC cells. Moreover, miR-431-5p could bind to ATF3, and overexpression of ATF3 rescued the effects mediated by miR-431-5p in TSCC cells. In addition, circ_0001742 regulated ATF3 expression through miR-431-5p. Our results demonstrated that circ_0001742 plays a tumor-promoting effect in TSCC cells by serving as a competing endogenous RNA (ceRNA) to regulate miR-431-5p/ATF3 axis, which might provide a potential therapeutic target for TSCC.

LncRNA CACS15 regulates tongue squamous cell carcinoma cell behaviors and predicts survival

BackgroundThe involvement of lncRNA CASC15 in several types of cancers has been reported, while its role in tongue squamous cell carcinoma (TSCC) is unknown. Our study aimed to investigate the clinical potentials of lncRNA CASC15 in TSCC.MethodsThe expression of CASC15 and miR-124 in tissue samples from TSCC patients and TSCC cell lines was analyzed by qPCR. Overexpression experiments were performed to analyze the interactions between CASC15 and miR-124. Survival analysis was performed to analyze the prognostic values of CASC15 and miR-124 for TSCC. Transwell assays were performed to analyze cell invasion and migration.ResultsWe found that CASC15 was upregulated, while miR-124 was downregulated in TSCC tissues than in non-cancer tissues of TSCC patients. CASC15 and miR-125 expression was not significantly different among patients with different clinical stages, and patients with high level of CASC15 and low level of miR-125 showed low overall survival rate. CASC15 and miR-124 were inversely correlated in TSCC tissues, and CASC15 overexpression in TSCC cells resulted in downregulation of miR-124. In contrast, overexpression of miR-124 showed no significant effect on CASC15 expression. CASC15 overexpression resulted in the increased, while miR-124 overexpression resulted in the decreased migration and invasion rates of TSCC cells.ConclusionCASC15 and miR-124 predict TSCC patients’ survival and CASC15 may downregulate miR-124 to inhibit TSCC cell migration and invasion.The study was approved by Ethics Committee of The first Affiliated Hospital of Jinzhou Medical University (20103548FAHJMU).

Expression and clinical value of PD-L1 which is regulated by BRD4 in tongue squamous cell carcinoma.

The programmed cell death-ligand-1 (PD-L1) and bromodomain protein 4 (BRD4) are frequently overexpressed in cancer and have even been shown to act synergistically. The aim of this study was to determine their potential oncogenic role .in tongue squamous cell carcinoma (TSCC). We detected significantly higher expression levels of both PD-L1 and BRD4 in TSCC tissues compared to normal tissues (P ≤ .05). In addition, the high levels of PD-L1 were significantly associated with increased tumor lymphatic metastasis (P ≤ .05), tumor staging (P ≤ .01), as well as BRD4 expression (P ≤ .05). Genetic and pharmacological inhibition of BRD4 in TSCC cells not only reduced their growth rate but also PD-L1 levels (P ≤ .05), while overexpression of BRD4 upregulated PD-L1. Bioinformatics analysis showed that c-MYC and CDK9 were interactive partners of both BRD4 and PD-L1. While c-MYC clearly modulated the expression of PD-L1, as well as reversed the inhibitory effects of JQ1, no obvious association was observed between CDK9 and PD-L1. We report a novel regulatory axis consisting of BRD4, PD-L1, and c-MYC that likely drives TSCC progression, and is a potential prognostic marker and/or therapeutic target for TSCC.

MiR-611 promotes the proliferation, migration and invasion of tongue squamous cell carcinoma cells by targeting FOXN3.

The function of miR-611 has not yet been reported. We aimed to investigate the effects of miR-611 on tongue squamous cell carcinoma (TSCC) and the underlying mechanism. The expression level of miR-611 in TSCC tissues was measured using quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). Cell proliferation, migration and invasion were examined by performing CCK-8, IncuCyte and Transwell assays. Bioinformatics analyses and microarrays were used to screen for target genes, which were verified using a luciferase reporter assay, RT-qPCR and Western blotting. The xenograft model was used to assess the effects of miR-611 in vivo. miR-611 was upregulated in TSCC tissues, which was significantly correlated with TNM stage and negatively associated with the overall survival of patients. In addition, upregulation of miR-611 not only potentiated the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of TSCC cells in vitro, but also promoted tumour growth in vivo. FOXN3 was identified as a candidate target gene of miR-611 and subsequently verified. Finally, miR-611 induced a malignant phenotype of TSCC, which was rescued by overexpression of FOXN3. Our findings suggest that miR-611 is a novel therapeutic target for TSCC.

MicroRNA-21-5p targeting PDCD4 suppresses apoptosis via regulating the PI3K/AKT/FOXO1 signaling pathway in tongue squamous cell carcinoma.

The aim of the present study was to analyze the role of microRNA (miRNA)-21-5p in tongue squamous cell carcinoma (TSCC), predict the target gene of miR-21-5p and provide novel strategies for gene therapy in TSCC treatment. The expression levels of miRNA-21-5p in TSCC tissues were analyzed using reverse transcription quantitative polymerase chain reaction, and the effects of miRNA-21-5p on cell proliferation, invasion and apoptosis and the expression levels of target protein PDCD4 in the Cal 27 and SCC9 cell lines were determined. PI3K/AKT/Forkhead Box O1 (FOXO1) pathway-associated protein expression levels were evaluated by western blot analysis. miRNA-21-5p was consistently upregulated in TSCC tissues compared with normal tissues. Inhibition of miR-21-5p inhibited cell proliferation and invasion, and promoted cell apoptosis. A luciferase reporter assay confirmed that PDCD4 was the target of miR-21-5p. Inhibition of miRNA21-5p suppressed the PI3K/Akt/FOXO1 signaling pathway. The results from the present study indicated that miR-21-5p-targeting PDCD4 suppresses apoptosis in human TSCC cell lines. This anti-apoptotic effect was achieved by regulating the PI3K/Akt/FOXO1 signaling pathway. These data represent the basis for a promising novel strategy for the treatment of TSCC.

MicroRNA-493 inhibits tongue squamous cell carcinoma oncogenicity via directly targeting HMGA2.

BackgroundsmicroRNA-493-3p (miR-493) has been reported to be critically downregulated in multiple types of human cancer. However, the expression level, biological roles and underlying mechanism of miR‑493 in tongue squamous cell carcinoma (TSCC) remain to be elucidated.MethodsRT-qPCR was utilized for the determination of miR-493 expression in TSCC tissues and cell lines. The influence of miR-493 overexpression on TSCC cell proliferation, apoptosis, migration, invasion in vitro and tumor growth in vivo were explored via MTT assay, flow cytometry analysis, cell migration and invasion assays, and xenograft tumors in nude mice, respectively. Bioinformatics analysis, luciferase reporter assays, RT-qPCR and Western blotting were performed to clarify the potential mechanisms involved in the action of miR-493 in TSCC cells.ResultsmiR-493 was significantly downregulated in TSCC tissues and cell lines. Decreased miR-493 expression was notably correlated with tumor differentiation, depth of invasion and TNM stage. Additionally, patients with TSCC having low miR-493 expression showed lower overall survival rate. Functionally, miR-493 upregulation inhibited TSCC cell proliferation, migration, invasion in vitro; induced cell apoptosis; and decreased the tumor growth in vivo. Bioinformatics analysis followed by luciferase reporter assays also demonstrated that miR-493 directly bound to the 3ʹ-untranslated region of high-mobility group AT-hook 2 (HMGA2) in TSCC cells, and therefore reduced HMGA2 expression at the mRNA and protein level. Furthermore, HMGA2 was overexpressed in TSCC tissues and inversely correlated with miR-493. Moreover, silenced HMGA2 expression simulated the tumor-suppressing roles of miR-493 overexpression on TSCC cells. HMGA2 overexpression eliminated the inhibitory roles of miR-493 overexpression on TSCC cells.ConclusionThese observations demonstrated that miR-493 is a tumor suppressor inhibited the oncogenicity of TSCC cells by directly targeting HMGA2. These results provide sufficient evidence for the miR-493/HMGA2 axis as a novel therapeutic target for the treatment of patients with TSCC in the future.

Tongue squamous cell carcinoma discrimination with Raman spectroscopy and convolutional neural networks

Discriminating the border of tongue squamous cell carcinoma (TSCC) is very critical for surgical treatment. Based on fiber optic Raman spectroscopy and deep learning technique, this study proposed a framework with convolutional neural networks (CNN) to discriminate TSCC from non-tumorous tissue. First, Raman spectra of 24 samples of TSCC and adjacent tissues from 12 patients were collected by fiber optic Raman spectroscopy system. Through the analysis, the significant differences between TSCC and non-tumorous tissue were occured in the range of 700–1800 cm−1. Then a CNN model was used to extract the nonlinear feature representations from Raman spectra. Finally, extracted features are fed into a fully-connected layer for TSCC classification. The results demonstrated that the CNN model obtained the sensitivity and specificity of 99.07% and 95.37%, respectively. Moreover, comparison results with existing methods showed our method achieved the highest accuracy of TSCC classification. Therefore, Raman spectroscopy combined with the CNN model has a great potential to provide a useful technique for the intraoperative evaluation of the margin of resection of oral tongue squamous cell carcinoma.

LncRNA THOR promotes tongue squamous cell carcinomas by stabilizing IGF2BP1 downstream targets

THOR, a highly conserved lncRNA, is potentially involved in various cancer development. However, its involvement in tongue squamous cell carcinoma (TSCC) remains unclear. The present study aims to explore the biological function and molecular mechanism of THOR in TSCC progression. The expressions of THOR and IGF2BP1 in TSCC tissues and adjacent non-cancerous tongue tissues (ANT) were examined through qRT-PCR. THOR levels were manipulated in TSCC cells to explore its function in cancer progression in vitro and in vivo, which were subsequently evaluated by CCK8, colony formation assay, flow cytometry, xenograft tumor assays. In situ hybridization, RIP and Western blot assay were performed to explore the underlying molecular mechanisms. We discovered that THOR and IGF2BP1 were dramatically upregulated in TSCC tissues. The expression of THOR is positively correlated with IGF2BP1 mRNA level. THOR mediated IGF2 expression via interacting with IGF2BP1, and affected the downstream MEK-ERK signaling pathway to regulate TSCC cells proliferation. THOR/IGF2BP1/IGF2-MEK-ERK axis regulated the proliferation of TSCC cells, implying that THOR would be a promising therapeutic target for TSCC patients.

Long non-coding RNA myocardial infarction associated transcript promotes epithelial-mesenchymal transition and is an independent risk factor for poor prognosis of tongue squamous cell carcinoma.

Long non-coding RNA myocardial infarction associated transcript (MIAT) has been suspected to be associated with poor prognosis in several malignancies. This study aims to investigate the association between MIAT expression levels and prognosis of tongue squamous cell carcinoma (TSCC). Expressions of MIAT in TSCC specimens, corresponding adjacent non-neoplastic tongue tissues, and serums collected from 116 TSCC patients were detected by Quantitative Real-Time PCR. Then, these patients were followed up for 12months after discharge. MIAT was suppressed and upregulated in TSCC cells, and then cell invasion and epithelial-mesenchymal transition (EMT) markers were analyzed. Myocardial infarction associated transcript expression level in TSCC specimen was upregulated compared to adjacent non-neoplastic tongue tissue and had a significant positive association with its level in serum. MIAT levels in both TSCC specimen and serum were correlated with cervical lymph node metastasis and histological grading of TSCC patients. Results of survival analysis showed that high expression levels of MIAT in both TSCC tissues and serums indicated higher mortality and shorter survival time of TSCC patients. Receiver operating characteristic curve analysis showed that there was no significant difference between MIAT in TSCC specimen and serum to differentiate death and non-death of TSCC patients. In vitro study showed that MIAT could induce invasion of TSCC cells by regulating expressions of EMT markers through activation of Wnt/β-catenin signaling pathway. Upregulated MIAT promoted EMT of TSCC cells through activation of Wnt/β-catenin signaling pathway and indicated a poor prognosis of TSCC, which may provide us a non-invasive approach to evaluate the prognosis of TSCC.

Long Noncoding RNA MPRL Promotes Mitochondrial Fission and Cisplatin Chemosensitivity via Disruption of Pre-miRNA Processing.

The overall biological roles and clinical significance of most long noncoding RNAs (lncRNA) in chemosensitivity are not fully understood. We investigated the biological function, mechanism, and clinical significance of lncRNA NR_034085, which we termed miRNA processing-related lncRNA (MPRL), in tongue squamous cell carcinoma (TSCC). LncRNA expression in TSCC cell lines with cisplatin treatment was measured by lncRNA microarray and confirmed in TSCC tissues. The functional roles of MPRL were demonstrated by a series of in vitro and in vivo experiments. The miRNA profiles, RNA pull-down, RNA immunoprecipitation, serial deletion analysis, and luciferase analyses were used to investigate the potential mechanisms of MPRL. We found that MPRL expression was significantly upregulated in TSCC cell lines treated with cisplatin and transactivated by E2F1. MPRL controlled mitochondrial fission and cisplatin sensitivity through miR-483-5p. In exploring the underlying interaction between MPRL and miR-483-5p, we identified that cytoplasmic MPRL directly binds to pre-miR-483 within the loop region and blocks pre-miR-483 recognition and cleavage by TRBP-DICER-complex, thereby inhibiting miR-483-5p generation and upregulating miR-483-5p downstream target-FIS1 expression. Furthermore, overexpression or knockdown MPRL altered tumor apoptosis and growth in mouse xenografts. Importantly, we found that high expression of MPRL and pre-miR-483, and low expression of miR-483-5p were significantly associated with neoadjuvant chemosensitivity and better TSCC patients' prognosis. We propose a model in which lncRNAs impair microprocessor recognition and are efficient of pre-miRNA cropping. In addition, our study reveals a novel regulatory network for mitochondrial fission and chemosensitivity and new biomarkers for prediction of neoadjuvant chemosensitivity in TSCC.These findings uncover a novel mechanism by which lncRNA determines mitochondrial fission and cisplatin chemosensitivity by inhibition of pre-miRNA processing and provide for the first time the rationale for lncRNA and miRNA biogenesis for predicting chemosensitivity and patient clinical prognosis.

Computer-assisted image analysis of the tumor microenvironment on an oral tongue squamous cell carcinoma tissue microarray

Oral tongue squamous cell carcinoma (OTSCC) displays variable levels of immune cells within the tumor microenvironment. The quantity and localization of tumor infiltrating lymphocytes (TILs), specific functional TIL subsets (e.g., CD8+), and biomarker-expressing cells (e.g., PD-L1+) may have prognostic and predictive value. The purpose of this study was to evaluate the robustness and utility of computer-assisted image analysis tools to quantify and localize immunohistochemistry-based biomarkers within the tumor microenvironment on a tissue microarray (TMA). We stained a 91-patient OTSCC TMA with antibodies targeting CD3, CD4, CD8, FOXP3, IDO, and PD-L1. Cell populations were segmented into epithelial (tumor) or stromal compartments according to a mask derived from a pan-cytokeratin stain. Definiens Tissue Studio was used to enumerate marker-positive cells or to quantify the staining intensity. Automated methods were validated against manual tissue segmentation, cell count, and stain intensity quantification. Univariate associations of cell count and stain intensity with smoking status, stage, overall survival (OS), and disease-free survival (DFS) were determined. Our results revealed that the accuracy of automated tissue segmentation was dependent on the distance of the tissue section from the cytokeratin mask and the proportion of the tissue containing tumor vs. stroma. Automated and manual cell counts and stain intensities were highly correlated (Pearson coefficient range: 0.46–0.90; p < 0.001). Within this OTSCC cohort, smokers had significantly stronger PD-L1 stain intensity and higher numbers of CD3+, CD4+ and FOXP3+ TILs. In the subset of patients who had received adjuvant radiotherapy, a higher number of CD8+ TILs was associated with inferior OS and DFS. Taken together, this proof-of-principle study demonstrates the robustness and utility of computer-assisted image analysis for high-throughput assessment of multiple IHC markers on TMAs, with potential implications for studies on prognostic and predictive biomarkers.

High expression of FMNL3 associates with cancer cell migration, invasion, and unfavorable prognosis in tongue squamous cell carcinoma.

The aim of this study was to ascertain the expression and role of FMNL3 in tongue squamous cell carcinoma (TSCC) tissues. Immunohistochemistry, qRT-PCR, and western blot were used to study the expression of FMNL3 in TSCC tissues and its adjacent normal tissues. The relationship between FMNL3 overexpression and various clinicopathological parameters and patients' survival were further assessed. Next, we applied SCC25 and UM1 cell lines to study the effect of FMNL3 on tumor cell proliferation, migration, and invasion by silencing FMNL3. In this study, we demonstrated that FMNL3 expression was notably upregulated in TSCC tissues and associated with poor prognosis. The Cox regression survival analyses identified FMNL3 as an important independent predictor for patients' overall survival. We found that FMNL3 silencing by siRNA inhibited SCC25 and UM1 cell migration an invasion. FMNL3 overexpression is related to the metastasis of TSCC and poor prognosis. High expression of FMNL3 may become a new potential prognostic biomarker for patients with TSCC.

Xenotropic and polytropic retrovirus receptor 1 (XPR1) promotes progression of tongue squamous cell carcinoma (TSCC) via activation of NF-\u03baB signaling

BackgroundXenotropic and polytropic retrovirus receptor 1 (XPR1), a previously identified cellular receptor for several murine leukemia viruses, plays a role in many pathophysiological processes. However, the role of XPR1 in human cancers has not yet been characterized.MethodsReal-time PCR and western blotting assay were used to measure the expression of XPR1 in tongue squamous cell carcinoma (TSCC) tissues. Expression of XPR1 and p65 in clinical specimens was analyzed using immunohistochemical assay. The function of XPR1 on progression of TSCC was explored using in vitro and in vivo experiments. The molecular mechanism by which XPR1 helps to cancer progression was investigated by luciferase reporter activity, ELISA, PKA activity assay, immunofluorescence, western blotting and qPCR assay.ResultsHerein, we find that XPR1 is markedly upregulated in TSCC tissues compared to normal tongue tissues. High expression of XPR1 significantly correlates with the malignant features and poor patient survival in TSCC. Ectopic expression of XPR1 increases, while silencing of XPR1 reduces the proliferation, invasion and anti-apoptosis capacities of TSCC cells. Importantly, silencing of XPR1 effectively inhibits the tumorigenecity of TSCC cells. Moreover, we identified that XPR1 increased the concentration of intracellular cAMP and activated PKA. Thus, XPR1 promoted phosphorylation and activation of NF-κB signaling, which is required for XPR1-mediated oncogenic roles and significantly correlates with XPR1 expression in clinical specimens.ConclusionsThese findings uncover a critical role of XPR1 in TSCC progression via activation of NF-κB, and suggest that XPR1 might be a potential prognostic marker or therapeutic target.

Long noncoding RNA LINC00961 inhibited cell proliferation and invasion through regulating the Wnt/β-catenin signaling pathway in tongue squamous cell carcinoma.

Tongue squamous cell carcinoma (TSCC) is the most frequent style of oral squamous cell carcinoma. However, the molecular mechanisms and function of LINC00961 in the TSCC progression remain unknown. In this study, we proved that LINC00961 expression was downregulated in TSCC cells (Tca8113, SCC1, SCC-4, and SCC-15) compared with normal tissue. In addition, we showed that LINC00961 expression was downregulated in TSCC samples compared with matched normal tissues. Moreover, ectopic expression of LINC00961 decreased TSCC cell growth and invasion and suppressed epithelial-mesenchymal transition in TSCC cell. Furthermore, we indicated that overexpression of LINC00961 decreased β-catenin expression. Knockdown of LINC00961 promoted cell proliferation and invasion partly via promoting the Wnt/β-catenin signaling pathway. These results suggested that LINC00961 was downregulated in TSCC tissues and acted as a tumor suppressor gene in the development of TSCC.

LncRNA ADAMTS9-AS2 promotes tongue squamous cell carcinoma proliferation, migration and EMT via the miR-600/EZH2 axis.

Long noncoding RNAs (lncRNAs) are a type of noncoding RNA transcript that are characterized by lack of protein-coding capacity. The vital role of lncRNAs in tongue squamous cell carcinoma (TSCC) is attracting increasing attention. In the present study, we identify a key lncRNA regulating TSCC metastasis and investigated the underlying mechanism. Our results indicate that the lncRNA ADAMTS9-AS2 is most significantly upregulated in TSCC tissues from patients with lymph node metastasis and is closely associated with poor prognosis. Furthermore, ADAMTS9-AS2 knockdown in TSCC cells leads to a inhibition of cell migration and invasion and reverses TGF-β1 induced EMT. ADAMTS9-AS2 knockdown also inhibits TSCC cell growth in vitro and in vivo. In addition, we show that ADAMTS9-AS2 is a cytoplasmic lncRNA that shares the miRNA response elements (MREs) of miR-600 with EZH2, which is confirmed by a luciferase reporter assay and AGO2-dependent RNA immunoprecipitation (RIP). In summary, our results demonstrate an explicit oncogenic role of ADAMTS9-AS2 in TSCC tumorigenesis via competition with miR-600, suggesting a new regulatory mechanism of ADAMTS9-AS2 and providing a potential therapeutic target for TSCC patients.