scholarly journals Identification and Validation of HOTAIRM1 as a Novel Biomarker for Oral Squamous Cell Carcinoma

2022 ◽  
Vol 9 ◽  
Author(s):  
Yixiu Yu ◽  
Jiamei Niu ◽  
Xingwei Zhang ◽  
Xue Wang ◽  
Hongquan Song ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Gene Set Enrichment Analysis ◽  
Bioinformatics Analyses ◽  
Gene Set

ORAL squamous cell carcinoma (OSCC) is a malignant tumor with the highest incidence among tumors involving the oral cavity maxillofacial region, and is notorious for its high recurrence and metastasis potential. Long non-coding RNAs (lncRNAs), which regulate the genesis and evolution of cancers, are potential prognostic biomarkers. This study identified HOTAIRM1 as a novel significantly upregulated lncRNA in OSCC, which is strongly associated with unfavorable prognosis of OSCC. Systematic bioinformatics analyses demonstrated that HOTAIRM1 was closely related to tumor stage, overall survival, genome instability, the tumor cell stemness, the tumor microenvironment, and immunocyte infiltration. Using biological function prediction methods, including Weighted gene co-expression network analysis (WGCNA), Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA), HOTAIRM1 plays a pivotal role in OSCC cell proliferation, and is mainly involved in the regulation of the cell cycle. In vitro, cell loss-functional experiments confirmed that HOTAIRM1 knockdown significantly inhibited the proliferation of OSCC cells, and arrested the cell cycle in G1 phase. At the molecular level, PCNA and CyclinD1 were obviously reduced after HOTAIRM1 knockdown. The expression of p53 and p21 was upregulated while CDK4 and CDK6 expression was decreased by HOTAIRM1 knockdown. In vivo, knocking down HOTAIRM1 significantly inhibited tumor growth, including the tumor size, weight, volume, angiogenesis, and hardness, monitored by ultrasonic imaging and magnetic resonance imaging In summary, our study reports that HOTAIRM1 is closely associated with tumorigenesis of OSCC and promotes cell proliferation by regulating cell cycle. HOTAIRM1 could be a potential prognostic biomarker and a therapeutic target for OSCC.

scholarly journals Circ_0000745 strengthens the expression of CCND1 by functioning as miR-488 sponge and interacting with HuR binding protein to facilitate the development of oral squamous cell carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kuangzheng Li ◽  
Xiaosheng Fan ◽  
Ziyi Yan ◽  
Jia Zhan ◽  
Fangyun Cao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Cycle Arrest ◽  
Squamous Cell ◽  
Cycle Arrest

Abstract Background The implication of circular RNAs (circRNAs) in human cancers has aroused much concern. In this study, we investigated the function of circ_0000745 and its potential functional mechanisms in oral squamous cell carcinoma (OSCC) to further understand OSCC pathogenesis. Methods The expression of circ_0000745, miR-488 and cyclin D1 (CCND1) mRNA was measured by quantitative real-time polymerase chain reaction (qPCR). Cell proliferation capacity was assessed by cell counting kit-8 (CCK-8) assay and colony formation assay. Cell cycle progression and cell apoptosis were determined by flow cytometry assay. The protein levels of CCND1, PCNA, Cleaved-caspase 3 and HuR were detected by western blot. Animal study was conducted to identify the role of circ_0000745 in vivo. The targeted relationship was verified by dual-luciferase reporter assay, pull-down assay or RNA immunoprecipitation (RIP) assay. Results The expression of circ_0000745 was increased in OSCC tissues and cells. Circ_0000745 downregulation inhibited OSCC cell proliferation and induced cell cycle arrest and apoptosis in vitro, as well as blocked tumor growth in vivo. MiR-488 was a target of circ_0000745, and circ_0000745 downregulation suppressed OSCC development by enriching miR-488. Besides, circ_0000745 regulated CCND1 expression by targeting miR-488. In addition, circ_0000745 regulated CCND1 expression by interacting with HuR protein. CCND1 knockdown also inhibited OSCC cell proliferation and induced cell cycle arrest and apoptosis in vitro, and CCND1 overexpression recovered the inhibitory effects on OSCC cell malignant behaviors caused by circ_0000745 downregulation. Conclusions Circ_0000745 regulated the expression of CCND1 partly by acting as miR-488 sponge and interacting with HuR protein, thus promoting the progression of 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 Kava constituents exert selective anticancer effects in oral squamous cell carcinoma cells in vitro

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Antonio Celentano ◽  
Callisthenis Yiannis ◽  
Rita Paolini ◽  
Pangzhen Zhang ◽  
Camile S. Farah ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Migration ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Vitro Assay ◽  
Anticancer Effects

Abstract Kava is a beverage made from the ground roots of the plant Piper Methysticum. Active compounds of Kava have previously been demonstrated to exert an antiproliferative effect through cell cycle arrest and promotion of apoptosis. Our aim was to investigate the in vitro effects of the main constituents derived from Kava on oral squamous cell carcinoma (OSCC) activity. Gas chromatography mass spectrometry (GCMS) was used to characterise the main constituents of two Kava preparations. Cell proliferation was assessed in two human OSCC cell lines (H400 and BICR56) and in normal oral keratinocytes (OKF6) treated with the identified Kava constituents, namely Flavokawain A (FKA), Flavokawain B (FKB), yangonin, kavain and methysticin using an MTS in vitro assay. Cell migration at 16 h was assessed using a Transwell migration assay. Cell invasion was measured at 22 h using a Matrigel assay. Cell adhesion was assessed at 90 min with a Cytoselect Adhesion assay. The two Kava preparations contained substantially different concentrations of the main chemical constituents. Treatment of malignant and normal oral keratinocyte cell lines with three of the identified constituents, 10 μg/ml FKA, 2.5 μg/ml FKB and 10 μg/ml yangonin, showed a significant reduction in cell proliferation in both H400 and BICR56 cancer cell lines but not in normal OKF6 cells. Remarkably, the same Kava constituents induced a significant reduction of OSCC cell migration and invasion. We have demonstrated, for the first time, that Kava constituents, FKA, FKB and yangonin have potential anticancer effects on OSCC. This highlights an avenue for further research of Kava constituents in the development of future cancer therapies to prevent and treat OSCC.

Knockdown of RNF2 enhances the radiosensitivity of squamous cell carcinoma in lung

2019 ◽  
Vol 97 (5) ◽  
pp. 589-599 ◽  
Author(s):  
Jie Yang ◽  
Fan Yu ◽  
Jinlei Guan ◽  
Tao Wang ◽  
Changjiang Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Apoptosis ◽  
X Ray ◽  
Stable Transfectants

A previous study has reported that knockdown of RING finger protein 2 (RNF2) increases the radiosensitivity of esophageal cancer cells both in vitro and in vivo. However, the effect of RNF2 knockdown on radiosensitivity in squamous cell carcinoma (SqCC) remains unknown. For this, NCI-H226 and SK-MES-1 cells were exposed to X-ray irradiation and then RNF2 levels were determined. RNF2 was knocked-down and stable transfectants were selected. Radiosensitivity, cell proliferation, apoptosis, cell cycle, and γ-H2AX foci formation were evaluated. Interaction among ataxia telangiectasia mutated protein (ATM), mediator of DNA damage checkpoint 1 (MDC1), and H2AX were examined. Xenograft models were used to explore the effect of RNF2 knockdown on radiosensitivity in vivo. The results showed that RNF2 expression was significantly increased by X-ray irradiation. RNF2 knockdown combined with X-ray irradiation markedly inhibited cell proliferation, caused cell cycle arrest at the G1 phase, and induced cell apoptosis. In addition, RNF2 knockdown enhanced the radiosensitivity of SqCC cells, inhibited irradiation-induced γ-H2AX foci formation, and impaired the interactions among ATM, MDC1, and H2AX. Furthermore, combination of RNF2 knockdown and X-ray irradiation suppressed tumor growth and promoted tumor cell apoptosis in vivo. RNF2 may be a new therapeutic target to enhance the radiosensitivity of SqCC cells in lung.

scholarly journals Apigenin impairs oral squamous cell carcinoma growth in vitro inducing cell cycle arrest and apoptosis

2013 ◽  
Vol 43 (5) ◽  
pp. 1675-1682 ◽  
Author(s):  
DANIELE MAGGIONI ◽  
WERNER GARAVELLO ◽  
ROBERTA RIGOLIO ◽  
LORENZO PIGNATARO ◽  
RENATO GAINI ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Cycle Arrest ◽  
Squamous Cell ◽  
Cycle Arrest

scholarly journals Identification of Cell cycle Gene Signatures Predicting Survival in Patients with Lung Squamous Cell Carcinoma

2019 ◽  
Author(s):  
Lei Zhang ◽  
Zhe Zhang ◽  
Zhenglun Yu
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Lung Squamous Cell Carcinoma ◽  
Gene Signature ◽  
Gene Set Enrichment Analysis ◽  
Test Series ◽  
Gene Signatures ◽  
Gene Set

Abstract Background:Lung cancer (LC) is one of the most important and common malignant tumors, and its incidence and mortality are increasing annually. Lung squamous cell carcinoma (LUSC) is the common pathological type of lung cancer. A small part of biomarkers have been confirmed to be related to the prognosis and survival by data excavation. However, the moderate forecast effect of a single gene biomarker is not accurate. Thus, we aimed to identify new gene signatures to better predict Lung squamous cell carcinoma ( LU SC). Methods : Using the mRNA-mining approach, we performed mRNA expression profiling in large lung squamous cell carcinoma cohorts (n= from The Cancer Genome Atlas (TCGA) database. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis(GSVA) were accomplished, and connections between genes and cell cycle were found in the Cox proportional regression model. Results : We have confirmed a set of four genes (CDKN1A, CHEK2, E2F4 and RAD21) that were importantly associated with overall survival (OS) in the test series. Based on the research of the four-gene signature, the patients in the test series could be divided into high-risk and low-risk teams. Additionally, multivariate Cox regression analysis revealed that the prognostic power of the four-gene signature is independent of the clinical factors. Conclusion : Our study demonstrated the connections between the four-gene signature and cell cycle. Novel insights into the research mechanisms of cell cycle was also revealed regarding the biomarkers of a poor prognosis for lung squamous cell carcinoma patients.

scholarly journals Aspirin is Involved in the Cell Cycle Arrest, Apoptosis, Cell Migration, and Invasion of Oral Squamous Cell Carcinoma

2018 ◽  
Vol 19 (7) ◽  
pp. 2029 ◽  
Author(s):  
Xiaoqi Zhang ◽  
Hao Feng ◽  
Ziyu Li ◽  
Jie Guo ◽  
Minqi Li
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Focal Adhesion ◽  
Squamous Cell ◽  
Enrichment Analysis ◽  
Migration And Invasion ◽  
Invasion And Migration

Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. In China, its 5-year survival rate is roughly 50%, owing to acquired chemotherapeutic resistance and metastasis of the disease. Accumulating evidence demonstrates that aspirin (ASA) acts as a preventive or therapeutic agent in multiple cancers; however, anti-tumor activities induced by aspirin are unclear in OSCC. To investigate the possible role of aspirin in OSCC development, we first employed bioinformatics to analyze the anti-OSCC effects of aspirin. We performed a genetic oncology (GO) enrichment analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID), and the protein–protein interaction (PPI) network analysis by Cytoscape for differentially expressed genes (DEGs). We also evaluated the potential effects of aspirin on cell proliferation, invasion, migration, and apoptosis in two well-characterized OSCC cell lines (TCA8113 and CAL27). The bioinformatic results revealed that aspirin could inhibit proliferation by blocking the cell cycle, and could reduce migration and invasion via the PI3K-Akt and focal adhesion pathways. We found that ASA could downregulate the OSCC cell proliferation colony formation, invasion, and migration, as well as upregulate apoptosis. Furthermore, we found that ASA suppressed the activation of the focal adhesion kinase (FAK) and the phosphorylation of Akt, NF-κB, and STAT3. Overall, our data suggested that ASA may be developed as a chemopreventive agent to effectively treat OSCC.

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.

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