Tongue Squamous Cell Carcinoma Cell Migration Research Articles

Early growth response 1 regulates dual‑specificity protein phosphatase 1 and inhibits cell migration and invasion of tongue squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the head and neck, and among the OSCCs, tongue squamous cell carcinoma (TSCC) is one of the most common types. Although therapy strategies have recently advanced, the prognosis of TSCC has not substantially improved. Metastasis is one of the main causes of patient mortality in TSCC; therefore, it is necessary to elucidate the mechanism by which TSCC metastasis is regulated. In the present study, the early growth response 1 (Egr-1) expression in TSCC was analyzed based on GEO datasets and the effect of Egr-1 in TSCC tumor cell migration and invasion was measured using Transwell assay. By overexpressing dual-specificity protein phosphatase 1 (DUSP1) in cells with Egr-1 knockdown using lentivirus infection, the role of DUSP1 in Egr-1-regulated TSCC cell migration and invasion was determined. By using luciferase and ChIP assays, the mechanism behind how DUSP1 is regulated by Egr-1 was detected. In the present study, it was demonstrated that Egr-1 was downregulated in TSCC and the knockdown of Egr-1 increased TSCC cell migration and invasion. The expression of Egr-1 was also correlated with DUSP1. The overexpression of DUSP1 in Egr-1 knockdown cells, reduced the level of cell migration and invasion. Furthermore, it was demonstrated that knockdown of Egr-1 inhibited the promoter activity of DUSP1 and the site through which Egr-1 regulates DUSP1 transcription was identified. In conclusion, the present study demonstrated that Egr-1 regulates TSCC cell migration and invasion through modulating DUSP1, suggesting the potential of Egr-1 and DUSP1 as therapy targets for TSCC.

Actin filament-associated protein 1-antisense RNA1 promotes the development and invasion of tongue squamous cell carcinoma via the AFAP1-AS1/miR-133a-5p/ZIC2 axis.

The present study aimed to explore the biological role and underlying mechanism of the long non-coding RNA actin filament-associated protein 1-antisense RNA1 (lncRNA AFAP1-AS1) in the progression of tongue squamous cell carcinoma (TSCC). A quantitative reverse transcriptase-PCR (RT-qPCR) was conducted to assess relative levels of the miR-133a-5p, lncRNAs AFAP1-AS1 and zinc finger family member 2 (ZIC2) in TSCC cell lines and specimens, whereas ZIC2 protein levels were measured using western blotting. After modifying the levels of expression of lncRNA AFP1-AS1, miR-133a-5p and ZIC2 using lentivirus or plasmid transfection, we examined AKT/epithelial-mesenchymal transition signaling pathway alterations, in vivo carcinogenesis of TSCC in nude mice and in vitro malignant phenotypes. A dual-luciferase reporter assay was conducted to confirm the targeting relationship between ZIC2 and miR-133a-5p, as well as between miR-133a-5p and lncRNA AFAP1-AS1. Based on The Cancer Genome Atlas (TCGA) database, we additionally validated AFP1-AS1. The potential biological pathway for AFP1-AS1 was investigated using gene set enrichment analysis (GSEA). We also evaluated the clinical diagnostic capacities of AFP1-AS1 and clustered the most potential biomarkers with the Mfuzz expression pattern. Finally, we also made relevant drug predictions for AFP1-AS1. In TSCC cell lines and specimens, lncRNA AFAP1-AS1 was upregulated. ZIC2 was upregulated in TSCC cells as a result of lncRNA AFAP1-AS1 overexpression, which also promoted TSCC cell migration, invasion, viability, and proliferation. Via the microRNA sponge effect, it was found that lncRNA AFAP1-AS1 could upregulate ZIC2 by competitively inhibiting miR-133a-5p. Interestingly, knockdown of ZIC2 reversed the biological roles of lncRNA AFAP1-AS1 with respect to inducing malignant phenotypes in TSCC cells. In addition, in vivo overexpression of lncRNA AFAP1-AS1 triggered subcutaneous tumor growth in nude mice implanted with TSCC cells and upregulated ZIC2 in the tumors. The TCGA database findings revealed that AFAP1-AS1 was significantly upregulated in TSCC specimens and had good clinical diagnostic value. The results of GSEA showed that peroxisome proliferator-activated receptor signaling pathway was significantly correlated with low expression of AFP1-AS1. Finally, the results of drug prediction indicated that the group with high AFAP1-AS1 expression was more sensitive to docetaxel, AZD4547, AZD7762 and nilotinib. The upregulation of lncRNA AFAP1-AS1, which increases TSCC cell viability, migration, proliferation and invasion via the AFAP1-AS1/miR-133a-5p/ZIC2 axis, aids in the progression of TSCC.

LncKRT16P6 promotes tongue squamous cell carcinoma progression by sponging miR‑3180 and regulating GATAD2A expression.

Tongue squamous cell carcinoma (TSCC) is characterized by a poor prognosis and its 5-year overall survival rate has not improved significantly. However, the precise molecular mechanisms underlying TSCC remain largely unknown. Through RNA screening, the present study identified a novel long noncoding RNA (lncRNA), keratin 16 pseudogene 6 (lncKRT16P6), which was upregulated in TSCC tissues and cell lines and associated with TSCC tumor stage and differentiation grade. Inhibition of lncKRT16P6 expression reduced TSCC cell migration, invasion and proliferation. lncKRT16P6 sponged microRNA (miR)-3180 and upregulated GATA zinc finger domain containing 2A (GATAD2A) expression. miR-3180 inhibition reversed the lncKRT16P6 depletion-induced attenuation of TSCC malignancy and GATAD2A depletion reversed the miR-3180 silencing-induced enhancement of TSCC malignancy. In summary, the present study revealed a potential competitive endogenous RNA (ceRNA) regulatory pathway in which lncKRT16P6 modulates GATAD2A expression by binding miR-3180, ultimately promoting tumorigenesis and metastasis in TSCC. Therefore, lncKRT16P6 may be used as a prognostic biomarker and therapeutic target for clinical intervention in TSCC.

The enhanced genomic 6\u2009mA metabolism contributes to the proliferation and migration of TSCC cells

In contrast to the well-established genomic 5-methylcytosine (5mC), the existence of N6-methyladenine (6 mA) in eukaryotic genomes was discovered only recently. Initial studies found that it was actively regulated in cancer cells, suggesting its involvement in the process of carcinogenesis. However, the contribution of 6 mA in tongue squamous cell carcinoma (TSCC) still remains uncharacterized. In this study, a pan-cancer type analysis was first performed, which revealed enhanced 6 mA metabolism in diverse cancer types. The study was then focused on the regulation of 6 mA metabolism, as well as its effects on TSCC cells. To these aspects, genome 6 mA level was found greatly increased in TSCC tissues and cultured cells. By knocking down 6 mA methylases N6AMT1 and METTL4, the level of genomic 6 mA was decreased in TSCC cells. This led to suppressed colony formation and cell migration. By contrast, knockdown of 6 mA demethylase ALKBH1 resulted in an increased 6 mA level, enhanced colony formation, and cell migration. Further study suggested that regulation of the NF-κB pathway might contribute to the enhanced migration of TSCC cells. Therefore, in the case of TSCC, we have shown that genomic 6 mA modification is involved in the proliferation and migration of cancer cells.

Cyclin-dependent kinase 5 promotes the growth of tongue squamous cell carcinoma through the microRNA 513c-5p/cell division cycle 25B pathway and is associated with a poor prognosis.

BackgroundThe objective of this study was to investigate the role and molecular mechanism of cyclin‐dependent kinase 5 (CDK5) in regulating the growth of tongue squamous cell carcinoma (TSCC).MethodsThe authors used multiple methods to detect the levels of CDK5 expression in samples of TSCC and to explore the relation between CDK5 expression and various clinicopathologic factors. In vivo and in vitro cell experiments were performed to detect the proliferation, invasion, and migration of TSCC cells with CDK5 knockdown or overexpression. These studies verified that CDK5 regulates the occurrence and development of TSCC cells through the microRNA 513c‐5p/cell division cycle 25B pathway.ResultsAn elevated level of CDK5 expression in TSCC tissues was identified as an independent risk factor affecting TSCC growth and patient prognosis. Patients who had TSCC with low levels of CDK5 expression had a higher survival rate than those with high levels. Knockdown of CDK5 reduced the proliferation, migration, and invasion of TSCC cells both in vitro and in vivo. In addition, the authors observed that CDK5 regulated the growth of TSCC through the microRNA 513c‐5p/cell division cycle C25B pathway.ConclusionsCDK5 functions as an oncogene in TSCC and might serve as a molecular marker for use in the diagnosis and treatment of TSCC.Lay Summary Tongue squamous cell carcinoma (TSCC) is 1 of the most common malignant tumors of the head and neck, and the survival rate of patients with tongue cancer has been very low.Therefore, it is important to study the molecular mechanism of TSCC progression to identify biomarkers that can be used to improve its clinical diagnosis and treatment.Cyclin‐dependent kinase 5 (CDK5) is an atypical member of the cyclin‐dependent kinase family and is involved in regulating the cell cycle.Changes in the cell cycle are of great significance for the occurrence and development of tumor cells; and, in recent years, increasing evidence has suggested that CDK5 exists in a disordered state in cancer cells.In this study, the authors demonstrate that CDK5 functions as an oncogene in TSCC and might serve as a molecular marker for use in the diagnosis and treatment of TSCC.

SNHG1/miR-194-5p/MTFR1 Axis Promotes TGFβ1-Induced EMT, Migration and Invasion of Tongue Squamous Cell Carcinoma Cells.

Tongue squamous cell carcinoma (TSCC) is a common malignancy with aggressive biological behaviors. Mitochondrial fission regulator 1 (MTFR1), is aberrantly expressed in head and neck squamous cell carcinoma (HNSC), but its role in TSCC remains unclear. We aimed to explore the role of MTFR1 in TSCC. The expression of long non-coding RNA small nucleolar RNA host gene 1 (SNHG1), microRNA-194-5p and MTFR1 in TSCC cells was measured by RT-qPCR. Luciferase reporter assay and RNA pull down assay were applied to confirm the binding capacity between miR-194-5p and SNHG1 (or MTFR1). TSCC cell invasion and migration were accessed by Transwell assays. The protein levels of MTFR1 and epithelial-mesenchymal transition (EMT) markers were examined by western blot. MTFR1 had high expression level in TSCC. MTFR1 knockdown inhibited transforming growth factor β1 (TGFβ1)-induced EMT, migration and invasion of TSCC cells in vitro. MiR-194-5p targeted MTFR1 and negatively regulated its expression. In addition, SNHG1 upregulated the expression of MTFR1 by binding with miR-194-5p. Importantly, SNHG1 promoted EMT, invasion and migration of TSCC cells by upregulating MTFR1. SNHG1/miR-194-5p/MTFR1 axis promotes TGFβ1-induced EMT, migration and invasion of cells in TSCC, which could be potential targets for treating TSCC patients.

IncRNA XIST Targets miR-124/JAG1 via CeRNA Mechanism to Facilitate the Migration and Proliferation of Tongue Squamous Cell Carcinoma.

This study was designed to characterize the effect of lncRNA XIST on the migration as well as proliferation of tongue squamous cell carcinoma (TSCC) and its associated molecular mechanisms. Chip-seq analysis screened the aberrant lncRNA in TSCC patients. CCK-8 and scratch experiment detected cell migration and proliferation in TSCC after lncRNA XIST inhibition. We predicted and verified lncRNA XIST target miRNA. CCK-8 and scratch test examined the cell migration and proliferation effects in TSCC after transfection of miR-124 mimics. Luciferase reporter experiment confirmed the interaction of miR-124 with JAG1. Western blot validated influence of lncRNA XIST on miR-124/JAG1 axis. We found that lncRNA XIST was up-regulated in TSCC patients, and it facilitated the TSCC cell migration and proliferation in vitro. lncRNA XIST regulated miR-124 expression through ceRNA mechanism. Up-regulating miR-124 significantly inhibited TSCC cell migration and proliferation. JAG1 acted as immediate target of miR-124. Moreover, lncRNA XIST targeted miR-124 to regulate JAG1 levels through the ceRNA mechanism. IncRNA XIST encourages TSCC migration and proliferation by modulating miR-124/JAG1 axis.

CCR7-CCL21 axis promotes the cervical lymph node metastasis of tongue squamous cell carcinoma by up-regulating MUC1

This study aims at investigating the potential role of MUC1 in CCR7-CCL21 axis-induced metastasis of tongue squamous cell carcinoma (TSCC).TSCC patients were selected for epidemiologic trends. The expression of CCR7 and MUC1 was detected via immunohistochemistry. SCC15 and CAL27 cells were induced by CCL21 and specific antibody to CCR7. Gene and protein expression was detected using qRT-PCR and western blotting. Migration and invasion capacities of TSCC cells were determined using wound healing and Transwell invasion assays.The male:female ratio of 78 patients was 1.6:1. Metastasis rate of cervical lymph nodes (CLNs) was 42.3%. CLN metastasis significantly correlated with T staging (P = 0.026), clinical staging (P = 0.024), and depth of invasion (DOI, P = 0.001). DOI significantly influenced CLN metastasis (P = 0.033, OR = 10.919) of TSCC, as did CCR7 (P = 0.041) and MUC1 (P = 0.026). The consistency of CCR7 and MUC1 expression was fairly good (Kappa = 0.683, P < 0.001). Reduced survival was significantly associated with higher expression of CCR7 (P = 0.039) and MUC1 (P = 0.030). CCL21 up-regulated MUC1 in SCC15 cells, which was inhibited when CCR7 was blocked. MUC1 positively correlated with TSCC cell migration and invasion.CCR7-CCL21 axis might promote CLN metastasis of TSCC by up-regulating MUC1. CCR7 and MUC1 show promise as potential biomarkers for TSCC treatment.

Death by histone deacetylase inhibitor quisinostat in tongue squamous cell carcinoma via apoptosis, pyroptosis, and ferroptosis

Tongue cancer is one of the most common oral malignancies. Quisinostat is a histone deacetylase inhibitor with antitumor activity. The aim of this study was to evaluate the effects of quisinostat on the viability of tongue squamous cell carcinoma (TSCC) cells (CAL-27, TCA-8113) in vitro and in vivo. Cell viability, cell morphological observation, scratch wound-healing assay, transwell migration assay, transmission electron microscope, flow cytometry and cellular reactive oxygen species were assessed in vitro. The results showed that quisinostat can significantly inhibit the viability, growth and migration of TSCC cells. And quisinostat could significantly induce TSCC cells apoptosis, pyroptosis, and ferroptosis. Quisinostat significantly inhibited tumor tissue growth in animal experiments. Up-regulation of the expression of Bax, cleaved-caspase3, caspase-1, p53, phospho-p53 and down-regulated of the expression of caspase-3, Bcl-2, GPX4 in cell lines and tumor tissues of nude mice were observed by Western blotting analysis. Up-regulation of the expression of caspase-1, Bax, cleaved-caspase3, p53 and down-regulated of the expression of ki67, caspase-3, Bcl-2, GPX4 in tumor tissues of nude mice were observed by immunohistochemistry. TUNEL analysis showed that quisinostat could increase the apoptosis rate in the tumor tissues of nude mice. Up-regulation of the expression of p53 and down-regulated expression of GPX4 in cell lines were observed by immunofluorescent staining, and the expression locations of p53 and GPX4 proteins in TSCC cells were observed. Based on these findings, quisinostat may be a potential drug for the treatment of tongue squamous cell carcinoma.

LncRNA PART1 Exerts Tumor-Suppressive Functions in Tongue Squamous Cell Carcinoma via miR-503-5p.

BackgroundTongue squamous cell carcinoma (TSCC) accounts for one-third of oral cancers. Previous studies had reported that lncRNA/miRNA regulated the biological behaviors of different cancer cells. However, the mechanisms of PART1 in regulating tumorigenesis and TSCC development via targeting miR-503-5p had not been studied.MethodsThe expressions of PART1 and miR-503-5p in tissues and cultured cell lines were detected by qRT-PCR. StarBase 3.0 was used to predict the binding sites of PART1, then dual-luciferase assay and RNA pull-down assay were executed to confirm whether miR-503-5p was a target of PART1. TSCC cells were co-transfected with PART1-overexpressed plasmid or miR-503-5p mimics in vitro, and the transfection efficiency was evaluated through qRT-PCR. Western blot was performed to assess the expressions of EMT-related proteins. CCK-8 and clone formation assays were conducted to detect cell proliferation, TUNEL assay was used to detect apoptosis, and transwell assay was executed to test migration and invasion.ResultsThe low PART1 expression and high miR-503-5p expression were found in TSCC tissues and cell lines (CAL-27 and SCC9). PART1 expression was positively correlated with patients’ prognosis. The targeting and binding relationship between PART1 and miR-503-5p was confirmed, and overexpressed PART1 diminished the expression of miR-503-5p as well. Moreover, PART1 facilitated apoptosis, inhibited proliferation, invasion and migration of TSCC cells, and these influences were impeded by miR-503-5p overexpression.ConclusionLncRNA PART1 played a cancer-suppressing role in TSCC by targeting miR-503-5p, which provided a potential target for TSCC treatment.

The effects of HBXIP on the biological functions of tongue squamous cell carcinoma cells and correlation with PI3K/Akt.

BackgroundTongue squamous cell carcinoma (TSCC) is the most malignant oral cancer, having a high mortality rate.MethodsThe effects of hepatitis B X-interacting protein (HBXIP) overexpression on the proliferation, migration, and invasion of TSCC cells were measured by micro-culture tetrazolium assay (MTT) assay, transwell assay and scratch test, respectively, and the effects of HBXIP mRNA overexpression on the protein expression levels of AKT, p-AKT, PI3K, p-PI3K and S100A4 were detected by western blotting.ResultsMTT assay showed that there were significantly more proliferating cells than in the experimental group. In the scratch test and transwell assay, the migration rate and the number of invading cells were remarkably greater in the experimental group. The expression levels of p-AKT, p-PI3K and S100A4 were increased in the experimental group after HBXIP overexpression.ConclusionsHBXIP mRNA overexpression can influence the proliferation, invasion, and migration of TSCC cells and promote their proliferation and migration by increasing the protein expression levels of p-AKT, p-PI3K and S100A4.

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).

Progress in the study of long noncoding RNA in tongue squamous cell carcinoma.

Tongue squamous cell carcinoma (TSCC) is the most common and highly malignant oral squamous cell carcinoma (OSCC) with lymph node metastasis or distant organ metastasis and, thus, low overall survival rates. Studies on the molecular mechanism of the biologic characteristics of TSCC and exploration of targeted therapies have become the frontiers in the research of this disease. Long noncoding RNA (lncRNA), a type of noncoding RNA, plays a key role in the occurrence and development of tumors. In recent years, more and more studies on lncRNA have been focusing on tongue cancer. lncRNA affects the proliferation, invasion, and migration of TSCC cells through a variety of methods and molecular mechanisms. With reference to recent reports, this article provides an overview of the molecular mechanisms of various lncRNAs and their functions in TSCC.

Long noncoding RNA FALEC inhibits proliferation and metastasis of tongue squamous cell carcinoma by epigenetically silencing ECM1 through EZH2.

Tongue squamous cell carcinoma (TSCC), the most common epithelial cancer identified in the oral cavity, has become one of the most common malignancies across the developing countries. Increasing evidence indicates that long non-coding RNAs (lncRNAs) serve as important regulators in cancer biology. The focally amplified long non-coding RNA in epithelial cancer (FALEC) was found downregulated in the tissues of tongue squamous cell carcinoma (TSCC) and was predicted to present a good prognosis by bioinformatics analysis. Experiments indicated that FALEC knockdown significantly increased the proliferation and migration of TSCC cells both in vitro and in vivo; however, FALEC overexpression repressed these malignant behaviors. RNA pull-down and RNA immunoprecipitation demonstrated that FALEC could recruit enhancer of zeste homolog 2 (EZH2) at the promoter regions of extracellular matrix protein 1 (ECM1), epigenetically repressing ECM1 expression. The data revealed that FALEC acted as a tumor suppressor in TSCC and may aid in developing a novel potential therapeutic strategy against TSCC.

SA45APPLYING GENETIC RISK SCORES TO AN ETHNICALLY DIVERSE SAMPLE OF POSTPARTUM WOMEN

Tongue squamous cell carcinoma (TSCC) is the most common and highly malignant oral squamous cell carcinoma (OSCC) with lymph node metastasis or distant organ metastasis and, thus, low overall survival rates. Studies on the molecular mechanism of the biologic characteristics of TSCC and exploration of targeted therapies have become the frontiers in the research of this disease. Long noncoding RNA (lncRNA), a type of noncoding RNA, plays a key role in the occurrence and development of tumors. In recent years, more and more studies on lncRNA have been focusing on tongue cancer. lncRNA affects the proliferation, invasion, and migration of TSCC cells through a variety of methods and molecular mechanisms. With reference to recent reports, this article provides an overview of the molecular mechanisms of various lncRNAs and their functions in TSCC.

Odd-skipped related transcription factor 1 (OSR1) suppresses tongue squamous cell carcinoma migration and invasion through inhibiting NF-κB pathway

Tongue squamous cell carcinoma (TSCC) is the most common cancers of oral, owing to the high invasive and metastatic ability, patients with TSCC have poor prognosis, it's important to explore the regulatory mechanism of TSCC invasion and metastasis. Previous studies suggest OSR1 suppresses the progression of gastric cancer and renal cell carcinoma, but its role in TSCC hasn’t been studied. Here, we found OSR1 was downregulated in TSCC cells and specimens, Transwell and 3D spheroid invasion assay suggested OSR1 overexpression inhibited TSCC cell migration and invasion, while its knockdown promoted TSCC cell migration and invasion. Mechanism analysis found OSR1 expression was negatively correlated with NF-κB pathway and its targets. Western blot and NF-κB activity analysis suggested OSR1 inhibited NF-κB activity. Double inhibition of OSR1 and NF-κB significantly inhibited TSCC cell migration and invasion. These findings suggested OSR1 inhibited TSCC cell migration and invasion through inhibiting NF-κB pathway.

C-reactive protein is associated with the development of tongue squamous cell carcinoma.

C-reactive protein (CRP) acts as a biomarker reflecting different degrees of inflammation. Accumulating reports have suggested that there is a close relationship between CRP and various cancers. However, the influence of CRP on the development of tongue squamous cell carcinoma (TSCC) remains unclear. The purpose of this study was to investigate the role of CRP in TSCC. The results of immunohistochemical staining and statistical analyses showed that CRP expression was associated with TSCC tumor size, lymph node metastasis and pathological differentiation. Cell Counting Kit-8 (CCK-8) assay revealed that CRP could enhance TSCC cell proliferation in a dose- and time-dependent manner. Moreover, with CRP stimulation, proliferating cell nuclear antigen (PCNA) expression patterns presented a notable time-dependent up-regulation. In addition, CRP could enhance the invasion and migration of TSCC cells, as revealed by transwell and wound-healing assays, respectively. Annexin V-FITC/PI staining showed that CRP could protect TSCC cells from starvation- and drug-induced apoptosis. With CRP stimulation, the protein expression levels of phosphorylated protein kinase B (pAkt), phosphorylated mammalian target of rapamycin (pmTOR) and phosphorylated S6 ribosomal protein (pS6) were significantly increased, as demonstrated by western blot analysis. Our data suggest that CRP may play an important role in the development of TSCC. Moreover, the biological effects of CRP on TSCC cells might be related to Akt, mTOR, and S6.

FoxM1 promotes epithelial-mesenchymal transition, invasion, and migration of tongue squamous cell carcinoma cells through a c-Met/AKT-dependent positive feedback loop.

Forkhead box protein M1 (FoxM1) has been associated with cancer progression and metastasis. However, the function of FoxM1 in tongue squamous cell carcinoma (TSCC) remains largely unknown. The purpose of this study was to determine the role of FoxM1 in regulation of epithelial-mesenchymal transition (EMT) and migration of TSCC cells. We found that FoxM1 induced EMT and increased invasion/migration capacity in SCC9 and SCC25 cells. FoxM1 stimulation increased c-Met, pAKT, and vimentin levels but decreased E-cadherin level. Chromatin immunoprecipitation assay established that FoxM1 is bound to the promoter of c-Met to activate its transcription. In turn, c-Met promoted the expression of FoxM1 and pAKT. Blocking AKT signaling attenuated the invasion and migration of SCC9 and SCC25 cells stimulated by FoxM1 or c-Met. These results indicate that a positive feedback loop controls the EMT and migration of TSCC cells induced by FoxM1 and c-Met through AKT. Furthermore, the expression levels of FoxM1, pAKT, and c-Met were found to significantly increase in TSCC tissues compared with normal tissues, and these three biomarkers were concomitantly expressed in TSCC tissues. Clinical association analyses indicated that the expression of FoxM1, c-Met, and pAKT was associated with clinicopathological characteristics of patients with TSCC including tumor stage, tumor size, and lymph node metastasis. Taken together, our findings suggest that FoxM1 promotes the EMT, invasion and migration of TSCC cells, and cross-talks with c-Met/AKT signaling to form a positive feedback loop to promote TSCC development.

14-3-3ζ silencing retards tongue squamous cell carcinoma progression by inhibiting cell survival and migration.

Our study aimed to investigate the isoform-specific distribution of 14-3-3 in tongue squamous cell carcinoma (TSCC) and their association with cancer progression, and to further discuss their roles in cancer cell survival. In this study, 42 TSCC specimens and their matched normal para-carcinoma sections were collected. The immunohistochemistry analysis identified that 14-3-3σ and ζ isoforms presented significantly higher expression in cancerous tissues compared with the matched normal tongue tissue sections. 14-3-3ζ expression was associated with tumor T stage, lymph node metastasis and poor prognosis of TSCC. In vitro study revealed that 14-3-3ζ silencing alleviated the proliferation and migration of TSCC cells while promoted cancer cell apoptosis. 14-3-3ζ could bind to and inactivate FOXO3a transcription factor, in turn leading to the movement of the 14-3-3ζ-FOXO3a complex from nucleus to cytoplasm, which was inhibited after 14-3-3ζ silencing. Both 14-3-3ζ and FOXO3a silencing increased caspase 3 and 9 activation, while reduced inner mitochondrial membrane potential. Collectively, 14-3-3ζ may serve as a hallmark and prognostic marker of TSCC. 14-3-3ζ can bind to the FOXO3a transcription factor to promote the export of the complex to the cytoplasm, leading to enhanced proliferation and migration of tongue cancer cells.

Overexpression of HMGA2 promotes tongue cancer metastasis through EMT pathway.

BackgroundMetastasis to long distance organs is the main reason leading to morality of tongue squamous cell carcinoma (TSCC); however, the molecular mechanisms are still unknown. High mobility group AT-hook 2 (HMGA2) is highly expressed in multiple metastatic carcinomas, in which it contributes to cancer progression, metastasis and poor prognosis by upregulating Snail expression and inducing epithelial mesenchymal transition (EMT). This study focuses on investigating the role and mechanism of regulation of HMGA2 in the metastasis of TSCC.MethodsHMGA2 mRNA and protein expression were examined in TSCC specimens by quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry (IHC). Western blotting, IHC and immunofluorescence were also used to measure the expression and localization of EMT marker E-Cadherin and Vimentin both in TSCC cells and tissues. Knockdown assay was performed in vitro in TSCC cell lines using small interfering RNAs and the functional assay was carried out to determine the role of HMGA2 in TSCC cell migration and invasion.ResultsTSCC mRNA and protein expression were significantly up-regulated in tumor tissues when compared to adjacent non-tumor tissues, and the overexpression of HMGA2 was closely correlated with lymph nodes metastasis. Clinicopathological analysis indicated that HMGA2 expression was associated with clinical stage (P = 0.001), lymph node metastasis (P = 0.000), histological differentiation (P = 0.002) and survival (P = 0.000). Silencing the HMGA2 expression in Cal27 and UM1 resulted in the inhibition of cell migration and invasion, meanwhile down-regulation of HMGA2 impaired the phenotype of EMT in TSCC cell lines and tissues. The Multivariate survival analysis indicates that HMGA2 can be an independent prognosis biomarker in TSCC.ConclusionOur findings demonstrate that HMGA2 promotes TSCC invasion and metastasis; additionally, HMGA2 is an independent prognostic factor which implied that HMGA2 can be a biomarker both for prognosis and therapeutic target of TSCC.