Identification of Novel Key Targets and Candidate Drugs in Oral Squamous Cell Carcinoma

2020 ◽  
Vol 15 (4) ◽  
pp. 328-337
Author(s):  
Juan Liu ◽  
Xinjie Lian ◽  
Feng Liu ◽  
Xueling Yan ◽  
Chunyan Cheng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Network Analysis ◽  
Virtual Screening ◽  
Oral Squamous Cell Carcinoma ◽  
Small Molecules ◽  
Cell Carcinoma ◽  
Candidate Genes ◽  
Squamous Cell ◽  
Drug Targets ◽  
Therapeutic Strategies

Background: Oral Squamous Cell Carcinoma (OSCC) is the most common malignant epithelial neoplasm. It is located within the top 10 ranking incidence of cancers with a poor prognosis and low survival rates. New breakthroughs of therapeutic strategies are therefore needed to improve the survival rate of OSCC harboring patients. Objective: Since targeted therapy is considered as the most promising therapeutic strategies in cancer, it is of great significance to identify novel targets and drugs for the treatment of OSCC. Methods: A series of bioinformatics approaches were launched to identify the hub proteins and their potential agents. Microarray analysis and several online functional activity network analysis were firstly utilized to recognize drug targets in OSCC. Subsequently, molecular docking was used to screen their potential drugs from the specs chemistry database. At the same time, the assessment of ligand-based virtual screening model was also evaluated. Results: In this study, two microarray data (GSE31056, GSE23558) were firstly selected and analyzed to get consensus candidate genes including 681 candidate genes. Additionally, we selected 33 candidate genes based on whether they belong to the kinases and transcription factors and further clustered candidate hub targets based on functions and signaling pathways with significant enrichment analysis by using DAVID and STRING online databases. Then, core PPI network was then identified and we manually selected GRB2 and IGF1 as the key drug targets according to the network analysis and previous references. Lastly, virtual screening was performed to identify potential small molecules which could target these two targets, and such small molecules can serve as the promising candidate agents for future drug development. Conclusion: In summary, our study might provide novel insights for understanding of the underlying molecular events of OSCC, and our discovered candidate targets and candidate agents could be used as the promising therapeutic strategies for the treatment of OSCC.

scholarly journals COMPUTATIONAL ANALYSIS OF COMPOUNDS FROM OCIMUM SANCTUM FOR ANTICANCER ACTIVITY AGAINST ORAL SQUAMOUS CELL CARCINOMA

2019 ◽  
Vol 12 (1) ◽  
pp. 168
Author(s):  
Ariya Ss ◽  
Baby Joseph ◽  
Santhanam Viijayasri ◽  
Waheeta Hopper
Keyword(s):  
Squamous Cell Carcinoma ◽  
Virtual Screening ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Anticancer Activity ◽  
Squamous Cell ◽  
Anticancer Agents ◽  
Growth Factor Receptor ◽  
Binding Energies ◽  
Ocimum Sanctum

Objective: The objectives of this research are to identify the potentials of active phytochemicals from Ocimum sanctum as anticancer agents, by inhibiting the epidermal growth factor receptor (EGFR), one of the highly expressed proteins inducing metastasis in oral squamous cell carcinoma (OSCC) as well as other cancers.Methods: The phytochemicals found in O. sanctum were identified and downloaded from online chemical databases. The target protein was retrieved from the Protein Data Bank. Virtual screening using glide protocols of high throughput virtual screening and molecular docking using standard precision and extra precision (XP) were carried out. The binding energies and the important physicochemical properties of the compounds were also determined.Results: A total number of 210 compounds from O. sanctum were screened against EGFR. Lipinski rule was followed to find the compounds with favorable drug absorptive properties. The shortlisted compounds, namely luteolin, apigenin, and isothymusin, possess high Glide scores (kcal/mol) of −9.98, −9.51, and −9.45 and binding energies (kcal/mol) of −42.63, −48.28, and −44.95, respectively.Conclusion: Among the three compounds, Isothymusin was not yet been reported to posess anticancer activity. Our study suggest this compound as a potential chemotherapeutic agent for treating OSCC. They function by inhibiting the activity of metastasis - inducing protein EGFR.

microRNAs: Small Molecules with a Potentially Role in Oral Squamous Cell Carcinoma

2012 ◽  
Vol 19 (7) ◽  
pp. 1285-1291 ◽  
Author(s):  
Carolina Cavalieri Gomes ◽  
Silvia Ferreira de Sousa ◽  
Ricardo Santiago Gomez
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Small Molecules ◽  
Cell Carcinoma ◽  
Squamous Cell

scholarly journals Identification of a Gene Prognostic Signature for Oral Squamous Cell Carcinoma by RNA Sequencing and Bioinformatics

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Yang-Yang Zhang ◽  
Ming-Hui Mao ◽  
Zheng-Xue Han
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Candidate Genes ◽  
Rna Sequencing ◽  
Squamous Cell ◽  
Risk Model ◽  
Ppi Network ◽  
Prognostic Signature

Objectives. Oral squamous cell carcinoma (OSCC) is the most common oral cancer and has a poor prognosis. We aimed to identify new biomarkers or potential therapeutic targets for OSCC. Materials and Methods. Four pairs of tumor and adjacent normal tissues were collected from OSCC patients, and differentially expressed genes (DEGs) were screened via high-throughput RNA sequencing (RNA-seq). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to analyze the DEGs. A protein-protein interaction (PPI) network was established with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database and Cytoscape, and two significant clusters were found. Candidate genes were screened by analyzing head and neck squamous cell carcinoma (HNSCC) data from The Cancer Genome Atlas (TCGA). A DEG-based risk model was established to predict the overall survival (OS) of OSCC patients via Kaplan-Meier analysis and the log-rank test. Furthermore, univariate Cox regression analysis was applied to assess associations between potential biomarkers and the overall survival rate. Results. Of 720 total DEGs, fifty-two DEGs in the two subclusters of the PPI network analysis were selected. A risk model was established, and five candidate genes (SPRR2E, ICOS, CTLA4, HTR1D, and CCR4) were identified as biomarkers of OS in OSCC patients. Conclusions. We successfully constructed a prognostic signature to predict prognosis and identified five candidate genes associated with the OS of OSCC patients that are potential tumor biomarkers and targets in OSCC.

scholarly journals PDK1 Inhibitor BX795 Improves Cisplatin and Radio-Efficacy in Oral Squamous Cell Carcinoma by Downregulating the PDK1/CD47/Akt-Mediated Glycolysis Signaling Pathway

2021 ◽  
Vol 22 (21) ◽  
pp. 11492
Author(s):  
Shin Pai ◽  
Vijesh Kumar Yadav ◽  
Kuang-Tai Kuo ◽  
Narpati Wesa Pikatan ◽  
Chun-Shu Lin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Strategies ◽  
Metabolic Reprogramming ◽  
Combination Group ◽  
Aberrant Expression ◽  
Mesenchymal Transition

Background: Oral squamous cell carcinoma (OSCC) has a high prevalence and predicted global mortality rate of 67.1%, necessitating better therapeutic strategies. Moreover, the recurrence and resistance of OSCC after chemo/radioresistance remains a major bottleneck for its effective treatment. Molecular targeting is one of the new therapeutic approaches to target cancer. Among a plethora of targetable signaling molecules, PDK1 is currently rising as a potential target for cancer therapy. Its aberrant expression in many malignancies is observed associated with glycolytic re-programming and chemo/radioresistance. Methods: Furthermore, to better understand the role of PDK1 in OSCC, we analyzed tissue samples from 62 patients with OSCC for PDK1 expression. Combining in silico and in vitro analysis approaches, we determined the important association between PDK1/CD47/LDHA expression in OSCC. Next, we analyzed the effect of PDK1 expression and its connection with OSCC orosphere generation and maintenance, as well as the effect of the combination of the PDK1 inhibitor BX795, cisplatin and radiotherapy in targeting it. Results: Immunohistochemical analysis revealed that higher PDK1 expression is associated with a poor prognosis in OSCC. The immunoprecipitation assay indicated PDK1/CD47 binding. PDK1 ligation significantly impaired OSCC orosphere formation and downregulated Sox2, Oct4, and CD133 expression. The combination of BX795 and cisplatin markedly reduced in OSCC cell’s epithelial-mesenchymal transition, implying its synergistic effect. p-PDK1, CD47, Akt, PFKP, PDK3 and LDHA protein expression were significantly reduced, with the strongest inhibition in the combination group. Chemo/radiotherapy together with abrogation of PDK1 inhibits the oncogenic (Akt/CD47) and glycolytic (LDHA/PFKP/PDK3) signaling and, enhanced or sensitizes OSCC to the anticancer drug effect through inducing apoptosis and DNA damage together with metabolic reprogramming. Conclusions: Therefore, the results from our current study may serve as a basis for developing new therapeutic strategies against chemo/radioresistant OSCC.

scholarly journals Identification and validation of key modules and hub genes associated with the pathological stage of oral squamous cell carcinoma by weighted gene co-expression network analysis

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8505 ◽  
Author(s):  
Xuegang Hu ◽  
Guanwen Sun ◽  
Zhiqiang Shi ◽  
Hui Ni ◽  
Shan Jiang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Network Analysis ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Pearson Correlation ◽  
Gene Set Enrichment Analysis ◽  
Hub Genes ◽  
T Stage

Background Oral squamous cell carcinoma (OSCC) is a major lethal malignant cancer of the head and neck region, yet its molecular mechanisms of tumourigenesis are still unclear. Patients and methods We performed weighted gene co-expression network analysis (WGCNA) on RNA-sequencing data with clinical information obtained from The Cancer Genome Atlas (TCGA) database. The relationship between co-expression modules and clinical traits was investigated by Pearson correlation analysis. Furthermore, the prognostic value and expression level of the hub genes of these modules were validated based on data from the TCGA database and other independent datasets from the Gene Expression Omnibus (GEO) database and the Human Protein Atlas database. The significant modules and hub genes were also assessed by functional analysis and gene set enrichment analysis (GSEA). Results We found that the turquoise module was strongly correlated with pathologic T stage and significantly enriched in critical functions and pathways related to tumourigenesis. PPP1R12B, CFD, CRYAB, FAM189A2 and ANGPTL1 were identified and statistically validated as hub genes in the turquoise module and were closely implicated in the prognosis of OSCC. GSEA indicated that five hub genes were significantly involved in many well-known cancer-related biological functions and signaling pathways. Conclusion In brief, we systematically discovered a co-expressed turquoise module and five hub genes associated with the pathologic T stage for the first time, which provided further insight that WGCNA may reveal the molecular regulatory mechanism involved in the carcinogenesis and progression of OSCC. In addition, the five hub genes may be considered candidate prognostic biomarkers and potential therapeutic targets for the precise early diagnosis, clinical treatment and prognosis of OSCC in the future.

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