scholarly journals Targeting of Survivin Pathways by YM155 Inhibits Cell Death and Invasion in Oral Squamous Cell Carcinoma Cells

2016 ◽  
Vol 38 (6) ◽  
pp. 2426-2437 ◽  
Author(s):  
Wei Zhang ◽  
Yuan Liu ◽  
Yu Feng Li ◽  
Yun Yue ◽  
Xinghua Yang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Growth ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Small Molecule ◽  
Squamous Cell ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Gene And Protein Expression

Background/Aims: Specific overexpression in cancer cells and evidence of oncogenic functions make Survivin an attractive target in cancer therapy. The small molecule compound YM155 has been described as the first “Survivin suppressant” but molecular mechanisms involved in its biological activity and its clinical potential remain obscure. Survivin protein plays critical roles in oral squamous cell carcinoma (OSCC), suggesting that YM155 would be extremely valuable for OSCC. In this study, we tested our hypothesis whether YM155 could be an effective inhibitor of cell growth, invasion and angiogenesis in oral squamous cell carcinoma (OSCC) cells. Methods: SCC9 and SCC25 were treated with different concentration of YM155 for indicated time. Using MTT assay and flow cytometry analysis to detect cell growth and apoptosis; Using transwell and Wound healing assay to detect migration and invasion; Using reverse transcription-PCR, Western blotting and electrophoretic mobility shift assay for measuring gene and protein expression, and DNA binding activity of NF-κB. Results: YM155 inhibited survivin-rich expressed SCC9 cell growth in a dose- and time dependent manner. This was accompanied by increased apoptosis and concomitant attenuation of NF-κB and downregulation of NF-κB downstream genes MMP-9, resulting in the inhibition of SCC9 cell migration and invasion in vitro and caused antitumor activity and anti metastasis in vivo. YM155 treatment did not affect cell growth, apoptosis and invasion of surviving-poor expressed SCC25 cells in vitro. Conclusions: YM155 is a potent inhibitor of progression of SCC9 cells, which could be due to attenuation of survivin signaling processes. Our findings provide evidence showing that YM155 could act as a small molecule survivin inhibitor on survivin-rich expressed SCC9 cells in culture as well as when grown as tumor in a xenograft model. We also suggest that survivin could be further developed as a potential therapeutic agent for the treatment of survivin-rich expressed OSCC.

The serum biomarker chemerin promotes tumorigenesis and metastasis in oral squamous cell carcinoma

2019 ◽  
Vol 133 (5) ◽  
pp. 681-695 ◽  
Author(s):  
Zhiyuan Lu ◽  
Jianfeng Liang ◽  
Qianting He ◽  
Quan Wan ◽  
Jinsong Hou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Migration And Invasion ◽  
Tumour Resection ◽  
Dependent Manner ◽  
Small Interfering Rnas ◽  
Malignant Tumours

AbstractChemerin, which is encoded by retinoic acid receptor responder 2 (RARRES2), has been found to be related to malignant tumours, but its role in the development of oral squamous cell carcinoma (OSCC) is largely unexplored. In the present study, a higher serum level of chemerin was evident in patients with OSCC than in healthy individuals, and this high level of chemerin significantly decreased after tumour resection. In addition, high chemerin levels were positively associated with advanced tumour stage and lymph node metastasis. The expression levels of chemerin and Chemerin Receptor 23 (ChemR23) were positively correlated with the migration and invasion of OSCC cell lines. Recombinant chemerin (R-chemerin) enhanced the in vitro migration, invasion and proliferation of OSCC cells in a concentration-dependent manner, and short hairpin RNAs (shRNAs) targeting RARRES2 decreased chemerin expression and inhibited OSCC cell metastasis and proliferation both in vitro and in vivo. Additionally, R-chemerin activated manganese superoxide dismutase (SOD2) and increased the amount of intracellular hydrogen peroxide (H2O2), leading to a significant decrease in E-cadherin expression and dramatic increase in the expression of phosphorylated ERK1/2 (p-ERK1/2), Slug, Vimentin and N-cadherin, but shRNAs targeting RARRES2 reversed these effects. Moreover, knockdown of ChemR23 with small interfering RNAs (siRNA) significantly inhibited chemerin-induced OSCC cell migration/invasion and SOD2 activity. Our results revealed that chemerin is a novel biomarker for OSCC. Chemerin/ChemR23 promotes tumorigenesis and metastasis in OSCC and may be a new therapeutic target for OSCC.

Cyclosporine A Suppresses the Malignant Progression of Oral Squamous Cell Carcinoma in vitro

2019 ◽  
Vol 19 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Ling Gao ◽  
Jianwei Dong ◽  
Nanyang Zhang ◽  
Zhanxian Le ◽  
Wenhao Ren ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cyclosporine A ◽  
Migration And Invasion ◽  
Signal Molecules ◽  
Cox 2

Background:The Oral Squamous Cell Carcinoma (OSCC) is one of the most frequent cancer types. Failure of treatment of OSCC is potentially lethal because of local recurrence, regional lymph node metastasis, and distant metastasis. Chemotherapy plays a vital role through suppression of tumorigenesis. Cyclosporine A (CsA), an immunosuppressant drug, has been efficiently used in allograft organ transplant recipients to prevent rejection, and also has been used in a subset of patients with autoimmunity related disorders. The present study aims to investigate novel and effective chemotherapeutic drugs to overcome drug-resistance in the treatment of OSCC.Methods:Cells were incubated in the standard way. Cell viability was assayed using the MTT assay. Cell proliferation was determined using colony formation assay. The cell cycle assay was performed using flow cytometry. Apoptosis was assessed using fluorescence-activated cell sorting after stained by the Annexin V-fluorescein isothiocyanate (FITC). Cell migration and invasion were analyzed using wound healing assay and tranwell. The effect of COX-2, c-Myc, MMP-9, MMP-2, and NFATc1 protein expression was determined using Western blot analysis while NFATc1 mRNA expression was determined by RT-PCR.Results:In vitro studies indicated that CsA inhibited partial OSCC growth by inducing cell cycle arrest, apoptosis, and the migration and invasion of OSCC cells. We also demonstrated that CsA could inhibit the expression of NFATc1 and its downstream genes COX-2, c-Myc, MMP-9, and MMP-2 in OSCC cells. Furthermore, we analyzed the expression of NFATc1 in head and neck cancer through the Oncomine database. The data was consistent with the experimental findings.Conclusion:The present study initially demonstrated that CsA could inhibit the progression of OSCC cells and can mediate the signal molecules of NFATc1 signaling pathway, which has strong relationship with cancer development. That explains us CsA has potential to explore the possibilities as a novel chemotherapeutic drug for the treatment of OSCC.

scholarly journals Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Wen Chen ◽  
Chenzhou Wu ◽  
Yafei Chen ◽  
Yuhao Guo ◽  
Ling Qiu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Endoplasmic Reticulum ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Endoplasmic Reticulum Stress ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Migration And Invasion ◽  
Ceramide Synthase

AbstractC18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma. However, the function of ceramide synthase 1, a key enzyme in C18 ceramide synthesis, in oral squamous cell carcinoma is still unclear. The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer. In this study, we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines. In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide, ceramide synthase 1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, ceramide synthase 1 knockdown promoted cell proliferation, migration, and invasion in vitro. Overexpression of CERS1 obtained the opposite effect. Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation. Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation. In addition, mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance. Taken together, our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.

scholarly journals lncRNA LINC01296 Promotes Oral Squamous Cell Carcinoma Development by Binding with SRSF1

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yanhui Zhang ◽  
Aifang Wang ◽  
Xiaohe Zhang ◽  
Xiaoliang Wang ◽  
Jin Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cervical Lymph Node Metastasis ◽  
Migration And Invasion ◽  
Clinical Samples

Objective. Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the head and neck, with strong local invasiveness and cervical lymph node metastasis. The purpose of this study was to investigate the role of LINC01296 in oral squamous cell carcinoma and its possible mechanism. Materials and Methods. GEPAI database analysis and clinical samples were used to detect the expression of LINC01296 in head and neck cancer. In vivo experiment, MTT, clone formation assay, and transwell were used to detect the proliferation, migration, and invasion of oral squamous cell carcinoma. The effect of LINC01296 on EMT was detected by western blot and qRT-PCR to measure the expression of epithelial and mesenchymal phenotypic markers. BALB/c nude mice were used to carry out in vitro treatment experiment. In terms of mechanism, the binding relationship between LINC01296 and SRSF1 was predicted and verified by the RBPDB database and RNA pull-down assay. Results. LINC01296 was highly expressed in clinical samples and cell lines of oral squamous cell carcinoma. Overexpression of LINC01296 promoted the proliferation, invasion, and migration of oral squamous cell carcinoma cells and accelerated the formation of xenografts, while silencing LINC01296 inhibited tumor progression. In mechanism, LINC01296 plays a tumor-promoting role by binding to SRSF1 protein. Conclusion. LINC01296 promotes malignant lesions in oral squamous cell carcinoma by binding to SRSF1 protein, which provides important experimental data and theoretical basis for the prevention, diagnosis, and treatment of oral squamous cell carcinoma.

METTL3 Promotes Oral Squamous Cell Carcinoma Progression by Enhancing SLC7A11 mRNA Stability via m6A-Mediated IGF2BP2 Binding

2021 ◽  
Author(s):  
Le Xu ◽  
Qingxiang Li ◽  
Yifei Wang ◽  
Lin Wang ◽  
Yuxing Guo ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Mrna Stability ◽  
Messenger Rna ◽  
Specific Treatment ◽  
Dependent Manner ◽  
Rna Seq

Abstract Background: As the key enzyme of the N6-methyladenosine (m6A) in eukaryotic messenger RNA, METTL3 plays important roles in tumor progression, but the exact mechanism by which METTL3 controls oral squamous cell carcinoma (OSCC) progression remains unclear. Methods: METTL3 expression in OSCC samples was analyzed by qPCR and immunohistochemistry. The effects of METTL3 suppression on OSCC cell lines were measured by CCK-8, Ki-67 flow cytometry analysis, invasion transwell and wound healing assays. MeRIP-seq and RNA-seq analysis were performed to explore target gene of METTL3. RIP-qPCR and RNA stability assays were performed to explore the mechanism by which METTL3 regulated the target genes. Triptolide was used to evaluate its specific treatment effects on METTL3 in OSCC cells. BALB/c nude mice were used to establish orthotopic and subcutaneous xenograft models to verify the in vitro results.Results: METTL3 was upregulated in OSCC tissues than adjacent normal tissues, and its expression was associated with T stage, lymphatic metastasis and prognosis. In vitro and in vivo studies suggested that METTL3 suppression impaired cell proliferation, invasion, and migration. MeRIP-seq and RNA-seq analysis identified that SLC7A11 mRNA was the m6A target of METTL3, which was verified by meRIP-qPCR, qPCR and western blot. METTL3 depletion decreased the stability of SLC7A11 mRNA, and IGF2BP2 was involved in this process. Moreover, METTL3 knockdown attenuated the binding between SLC7A11 mRNA and IGF2BP2, finally leading to accelerate SLC7A11 mRNA degradation. Triptolide inhibited METTL3 and SLC7A11 expression in a dose-dependent manner, thus suppressing malignancy of OSCC cells. Conclusions: METTL3 enhances the mRNA stability of SLC7A11 via m6A-mediated binding of IGF2BP2, which thus promotes OSCC progression, and triptolide inhibits OSCC by suppressing METTL3-SLC7A11 axis.

scholarly journals JQ1, a small molecule inhibitor of BRD4, suppresses cell growth and invasion in oral squamous cell carcinoma

2016 ◽  
Vol 36 (4) ◽  
pp. 1989-1996 ◽  
Author(s):  
Limei Wang ◽  
Xiuyin Wu ◽  
Ping Huang ◽  
Zhijun Lv ◽  
Yuping Qi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Growth ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Small Molecule ◽  
Squamous Cell ◽  
Small Molecule Inhibitor ◽  
Molecule Inhibitor

Ral GTPase Activation by Downregulation of RalGAP Enhances Oral Squamous Cell Carcinoma Progression

2019 ◽  
Vol 98 (9) ◽  
pp. 1011-1019 ◽  
Author(s):  
P. Gao ◽  
S. Liu ◽  
R. Yoshida ◽  
C.Y. Shi ◽  
S. Yoshimachi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Migration And Invasion ◽  
Activation Level ◽  
Ral Gtpase

Ral small GTPases, consisting of RalA and RalB, are members of the Ras family. Their activity is upregulated by RalGEFs. Since several RalGEFs are downstream effectors of Ras, Ral is activated by the oncogenic mutant Ras. Ral is negatively regulated by RalGAP complexes that consist of a catalytic α1 or α2 subunit and its common partner β subunit and similarly regulate the activity of RalA as well as RalB in vitro. Ral plays an important role in the formation and progression of pancreatic and lung cancers. However, the involvement of Ral in oral squamous cell carcinoma (OSCC) is unclear. In this study, we investigated OSCC by focusing on Ral. OSCC cell lines with high Ral activation exhibited higher motility. We showed that knockdown of RalGAPβ increased the activation level of RalA and promoted the migration and invasion of HSC-2 OSCC cells in vitro. In contrast, overexpression of wild-type RalGAPα2 in TSU OSCC cells attenuated the activation level of RalA and inhibited cell migration and invasion. Real-time quantitative polymerase chain reaction analysis of samples from patients with OSCC showed that RalGAPα2 was downregulated in oral cancer tissues as compared with normal epithelia. Among patients with OSCC, those with a lower expression of RalGAPα2 showed a worse overall survival rate. A comparison of DNA methylation and histone modifications of the RalGAPα2 gene in OSCC cell lines suggested that crosstalk among DNA methylation, histone H4Ac, and H3K27me2 was involved in the downregulation of RalGAPα2. Thus, activation of Ral GTPase by downregulation of RalGAP expression via a potential epigenetic mechanism may enhance OSCC progression.

scholarly journals miR-146b Functions as an Oncogene in Oral Squamous Cell Carcinoma by Targeting HBP1

2020 ◽  
Vol 19 ◽  
pp. 153303382095940
Author(s):  
Kui Li ◽  
Zheng Zhou ◽  
Ju Li ◽  
Rui Xiang
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Target Prediction ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
The Impact

Oral squamous cell carcinoma (OSCC) represents more than 90% of all oral cancer and is the most common oral threat around the world. In this study, we examined the roles of miR-146b in OSCC cells. The miR-146b expression in OSCC tissues and cell lines was evaluated by quantitative real-time PCR (qRT-PCR). MTT assay was used to investigate the impact of miR-146b on the growth of OSCC cells in vitro. Transwell assay was utilized to analyze the effect of miR-146b on the migration and invasion of OSCC cells. Target prediction and luciferase assay were employed to demonstrate the interaction between miR-146b and HMG-Box Transcription Factor 1 (HBP1). Western blot was carried out to investigate the protein expressions of HBP1 related genes. miR-146b expression was significantly higher in OSCC tissues and cells compared with paired normal tissues and normal oral keratinocyte cells. Inhibition of miR-146b decreased cell proliferation, migration, and invasion of OSCC cells. Further studies found that HBP1 was a direct target of miR-146b. Co-inhibition of HBP1 reversed the suppressive impact of miR-146b inhibition on OSCC cell proliferation, migration, and invasion. In conclusion-ourresults reveal that miR-146b potentially regulates the proliferation, migration, and invasion of OSCC cells through binding and downregulating HBP1 expression in OSCC cells.

Inhibition of Angiogenesis and Tumor Progression of Mk-0429, an Integrin Αvβ3 Antagonist, on Oral Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Takayuki Nakagawa ◽  
Kouji Ohta ◽  
Takako Naruse ◽  
Miyuki Sakuma ◽  
Satoshi Okuda ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Tumor Progression ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tube Formation ◽  
Dependent Manner ◽  
Dose Dependent

Abstract PurposeIntegrin αvβ3 is an essential molecule for tumor angiogenesis. This study aimed to investigate the anti-tumor effect of MK-0429, an integrin αvβ3 antagonist, on oral squamous cell carcinoma (OSCC) through its inhibitory effect on angiogenesis.MethodsIn this study, we investigated the effect of MK-0429 on cellular function and angiogenesis in vitro with the use of an immortalized human umbilical vein endothelial cell, HUEhT-1, which is immortalized by the electroporatic transfection of hTERT. The effect of MK-0429 on the integrin αvβ3 signaling pathway was examined by FAK and ERK 1/2 phosphorylation. The anti-angiogenic effect of MK-0429 was evaluated by in vitro tube formation assay. The anti-tumor effect on OSCC was assessed by administrating MK-0429 to mouse oral cancer xenografts.ResultsMK-0429 inhibited cell proliferation, migration, and adhesion of HUEhT-1 in a dose-dependent manner. FAK and ERK phosphorylation were significantly blocked by MK-0429 treatment. Tube formation was suppressed by MK-0429 in dose-dependent manner. Tumor progression was significantly suppressed by MK-0429 administration in mouse oral cancer xenografts. Histological study revealed that MK-0429 decreased tumor vascularization.ConclusionThese results indicated integrin αvβ3 as a therapeutic target for OSCC and suggested that MK-0429 might be clinically applicable as an anti-tumor agent with potent antiangiogenic activity.

Sign in / Sign up

Export Citation Format

Share Document