Gene expression in cancerous and paraneoplastic tissues of patients with head and neck squamous cell carcinoma.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE228393 | GEO | 2023/03/28
REPOSITORIES: GEO
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Project description:Objective: Head and neck squamous cell carcinoma (HNSCC) is one severe malignancy driven by complex cellular and signaling mechanisms. However, the roles of circular RNAs (circRNAs) in HNSCC’s development remains poorly understood. Therefore, this study investigated the functions of differentially expressed circRNAs in regulating HNSCC cell functions. Methods: Differentially expressed circRNAs were characterized through RNA sequencing in HNSCC tissues. CircRNA’s identity was then confirmed using RT-PCR and Sanger’s sequencing. Next, expression levels of circRNA and mRNA were detected by qRT-PCR, after which protein abundances were measured by Western blotting. Subsequently, the proliferation, migration, and invasion of HNSCC cells was assessed by MTS, wound healing, and Transwell system, respectively, followed by identification of circRNA-binding proteins in HNSCC cells by circRNA pull-down, coupled with mass spectrometry. Results: Great alterations in circRNA profiles were detected in HNSCC tissues, including the elevated expression of circ_0000045. As observed, silencing of circ_0000045 effectively repressed the proliferation, migration, and invasion of HNSCC cell lines (FaDu and SCC-9). Contrarily, circ_0000045’s overexpression promoted the proliferation, migration, and invasion in FaDu and SCC-9 cells. Results also showed that circ_0000045 was associated with multiple RNA-binding proteins in HNSCC cells, such as HSP70. Moreover, circ_0000045 knockdown enhanced HSP70 expression and promoted JNK2 and P38’s expression in HNSCC cells, which were oppositely regulated by circ_0000045’s overexpression. Conclusion: The high expression of circ_0000045; therefore, promoted cell proliferation, migration, and invasion during HNSCC’s development through association with HSP70 protein to activate mitogen-activated protein kinase signaling.
2022-05-11 | GSE197138 | GEO
Project description:Profiling the genome-wide methylation status of head and neck squamous cell carcinoma and normal subjects Screening HNSCC-related candidate methylation gene by comparison of HNSCC tissues vs normal subjects.
2014-06-19 | E-GEOD-58630 | biostudies-arrayexpress
Project description:To identify the activated tyrosine kinase signaling pathways in HNSCC, we carried out phosphotyrosine profiling using a panel of HNSCC cell lines compared to a normal oral keratinocyte. A total of 61 unique phosphosites were identified across these cell lines. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) was one of the kinases hyperphosphorylated at Y321 in all the HNSCC cell lines compared to the normal oral cell line OKF6/TERT1. Inhibition of DYRK1A using its specific siRNA and inhibitor resulted in a decrease in the invasion and colony formation ability of the HNSCC cell lines. Further, the treatment of mice bearing HNSCC xenograft tumors with DYRK1A inhibitor (harmine) showed regression of tumor growth. Our results demonstrate that DYRK1A could be a novel therapeutic target in HNSCC.
2018-10-24 | PXD002132 | Pride
Project description:Aberrant activation of splicing regulators contributes to oncogenic transformation of cells by modulating the alternative splicing events of key oncogenes. Phosphorylation of splicing factors affects subcellular localization and activity of these proteins. Studies have shown a close association between altered phosphorylation of molecules involved in splicing machinery and cancer. We carried out proteomic and phosphoproteomic analysis of head and neck squamous cell carcinoma (HNSCC) cell lines using tandem mass tag (TMT) labeling approach followed by titanium dioxide-based phosphopeptides enrichment method. LC-MS/MS analysis resulted in the identification of 4,920 phosphosites corresponding to 2,288 proteins in six HNSCC cell lines compared to a normal oral cell line; OKF6/TERT1. Among the proteins identified, 23 kinases were found to be hyperphosphorylated in all HNSCC cell lines compared to the normal oral cell line.
2018-10-24 | PXD001862 | Pride
Project description:This SuperSeries is composed of the following subset Series: GSE11929: Identification of a subgroup of head and neck cancers lacking numerical chromosomal aberrations GSE11931: Copy Number Alterations in HNSCC with or without Oncogene Expressing Human Papillomavirus Refer to individual Series
2009-03-11 | E-GEOD-12020 | biostudies-arrayexpress
Project description:The bromodomain and extraterminal family members are epigenetic readers and transcriptional coactivators which are critically involved in various biological processes including tumorigenesis. BRD4 has been increasingly appreciated as a key oncogene and promising anticancer target. Here, we sought to characterize the expression of BRD4 and its tumorigenic roles as well as therapeutic targeting in HNSCC. Expression of BRD4 mRNA and protein was determined by bioinformatics interrogation of public available databases, primary HNSCC samples and 4NQO-induced HNSCC animal model. The tumorigenic roles of BRD4 in HNSCC were evaluated by genetic and pharmacological approach in vitro and in vivo. Therapeutic efficiency of BRD4 targeting by JQ1 was assessed in three preclinical models including xenograft model, 4NQO-induced model and patients-derived xenograft model. Gene candidates responsible for therapeutic effects of JQ1 were identified by transcriptional profiling in HNSCC cells after JQ1 exposure. Significant upregulation of BRD4 was found in primary HNSCC samples and 4NQO-induced HNSCC model. Its overexpression associated with aggressive clinicopathological features and inferior overall and disease-free survival. BRD4 depletion by genetic silencing or pharmacological inhibition impaired cell proliferation, migration and invasion and reduced tumor growth and metastasis in vivo. Transcriptional profiling of HNSCC cells following JQ1 exposure identified hundreds of genes which might mediated its antitumor effects and enriched in cancer-relevant pathways. A novel prognostic risk score derived from JQ1-regualted genes was developed to stratify patients into subgroups with favorable or inferior prognosis. Our findings reveal that BRD4 serves as a novel oncogene driving cancer progression and a robust prognostic biomarker in HNSCC. Therapeutic targeting of BRD4 represents a potent and promising strategy against HNSCC.
2019-05-09 | GSE122522 | GEO
Project description:The involvement of microRNAs (miRNAs) in cancer and their potential as biomarkers of diagnosis, prognosis and response to therapy is becoming increasingly appreciated. The etiology of head and neck squamous cell carcinoma (HNSCC) is predominantly associated with the synergistic effects of tobacco and alcohol use, as well as Human Papilloma Virus (HPV) infection, which embodies a distinct clinical and biological phenotype. We sought to examine whether the profile of miRNAs in HNSCC varies based on HPV status, and to identify specific miRNAs altered in head and neck carcinogenesis. Total RNA was isolated from 16 HNSCC fresh frozen primary tumors, 5 fresh frozen non-diseased head and neck epithelial tissues, and 2 HNSCC cell lines. The miRNA profile of 662 individual miRNAs in these tissues was examined by microarray. 18 miRNAs are significantly altered in their expression between normal tissues and HNSCC tumors and 5 miRNAs are identified as significantly differentially expressed between HPV-positive (HPV+) and HPV-negative (HPV-) tumors. A striking difference in expression pattern of miRNA was also observed between primary tissues and cell lines. These data suggest that the pattern of miRNA expression may be reflective of disease etiology, and may be useful in the realm of diagnostic biomarkers defining broadly responsive prevention and treatment strategies for HNSCC. These data also suggest that cultured tumor cell lines may be inappropriate for novel miRNA biomarker identification. Keywords: miRNA; Disease-state analysis Expression of 662 individual miRNA was assessed in16 HNSCC fresh frozen primary tumors, 5 fresh frozen non-diseased head and neck epithelial tissues, and 2 HNSCC cell lines were arrayed
2010-05-19 | E-GEOD-11163 | biostudies-arrayexpress
Project description:Highly coordinated, deregulated expressions of microRNAs (miRNA) have been implicated in the development of various cancers, including head and neck squamous cell carcinoma (HNSCC). Outside of HPV infection, molecular classification of HNSCC is lacking, and patient stratification by anatomical location and stage does not account for the heterogenous clinical courses seen. Previous studies have proposed molecular classifications based on gene expression, but none describe the role of microRNA expression in HNSCC subtyping. In this study, we identified reliable miRNA clusters that can be used to subclassify HNSCC tumors as well as other squamous tumors of other anatomic locations. An institutional discovery cohort was generated using miRNA expression data from microarrays, and this was validated using publicly available next-generation microRNA sequencing data from TCGA. Further analysis of these subtypes revealed distinct biological and clinical features of HNSCC tumors based on the miRNA expression profiles, which provides new insights into the pathogenesis and treatment of HNSCC.
2020-04-01 | GSE144711 | GEO
Project description:To identifythe the functional roles of circRNAs in human colorectal cancer, we analysed the differenial expression of circRNAs in 5 colorectal cancer tissues and the corresponding non-cancerous tissues. We used microarrays to detail the global programme of circRNA expression in human colorectal cancer tissues and correponding non-cancerous tissues.
2020-01-03 | GSE142837 | GEO
Project description:Analysis of different LncRNA expression in 4 paired metastatic HNSCC and non-metastatic HNSCC samples
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