Altered Epigenetic Regulation of Homeobox Genes in Human Oral Squamous Cell Carcinoma Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE51415 | GEO | 2013/10/19
SECONDARY ACCESSION(S): PRJNA222994
REPOSITORIES: GEO
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Project description:To gain insight into the molecular changes during OSCC carcinogenesis, we performed unbiased, whole genome deep sequencing (RNA-seq) using RNA isolated from cultured, human TERT-immortalized, non-tumorigenic OKF6-TERT1R and OSCC SCC-9 cells. OKF6-TERT1R cells and SCC-9 cells were plated in 10 cm2 tissue culture plates at the density of 2 × 106 cells/plate and treated with 1 μM RA or vehicle (0.1% ethanol) for 48 hours. Experiment includes 3 independent biological replicates. Note: All samples in SRA were assigned the same sample accession (GSM1245064 1). This is incorrect as there are different samples, hence “Source Name” was replaced with new values. Comment[ENA_SAMPLE] contains the original SRA sample accessions.
2013-10-19 | E-GEOD-51415 | biostudies-arrayexpress
Project description:To gain insight into the DNA methylation changes during OSCC carcinogenesis, we utilized cytosine conversion and next generation sequencing based technique- enhanced reduced representation bisulfite sequencing (ERRBS) - to assess DNA methylation in cultured, human TERT-immortalized, non-tumorigenic OKF6-TERT1R and OSCC SCC-9 cells. OKF6-TERT1R cells and SCC-9 cells were plated in 10 cm2 tissue culture plates at the density of 2 M-CM-^W 106 cells/plate. Total genomic DNA was extracted from OKF6-TERT1R and SCC-9 cells using DNeasy Blood & Tissue Kit (Qiagen, Germantown, MD, USA), including an RNAse treatment step.
2014-10-28 | E-GEOD-51752 | biostudies-arrayexpress
Project description:To gain insight into the DNA methylation changes during OSCC carcinogenesis, we utilized cytosine conversion and next generation sequencing based technique- enhanced reduced representation bisulfite sequencing (ERRBS) - to assess DNA methylation in cultured, human TERT-immortalized, non-tumorigenic OKF6-TERT1R and OSCC SCC-9 cells.
2014-10-28 | GSE51752 | GEO
Project description:Oral squamous cell carcinoma (OSCC) is a prevalent form of cancer that develops from the epithelium of the oral cavity. OSCC is on the rise worldwide, and death rates associated with the disease are particularly high. Despite progress in understanding of the mutational and expression landscape associated with OSCC, advances in deciphering these alterations for the development of therapeutic strategies have been limited. Further insight into the molecular cues that contribute to OSCC is therefore required. Here we show that the transcriptional regulators YAP (YAP1) and TAZ (WWTR1), which are key effectors of the Hippo pathway, drive pro-tumorigenic signals in OSCC. Regions of pre-malignant oral tissues exhibit aberrant nuclear YAP accumulation, suggesting that dysregulated YAP activity contributes to the onset of OSCC. Supporting this premise, we determined that nuclear YAP and TAZ activity drives OSCC cell proliferation, survival, and migration in vitro, and is required for OSCC tumor growth and metastasis in vivo. Global gene expression profiles associated with YAP and TAZ knockdown revealed changes in the control of gene expression implicated in pro-tumorigenic signaling, including those required for cell cycle progression and survival. Notably, the transcriptional signature regulated by YAP and TAZ significantly correlates with gene expression changes occurring in human OSCCs identified by The Cancer Genome Atlas (TCGA), emphasizing a central role for YAP and TAZ in OSCC biology. Expression profiling was conducted following the repression of the transcriptional regulators TAZ and YAP (YAP/TAZ) in human SCC2 oral cancer cells.
2015-05-26 | GSE66949 | GEO
Project description:Oral squamous cell carcinoma (OSCC) is a prevalent form of cancer that develops from the epithelium of the oral cavity. OSCC is on the rise worldwide, and death rates associated with the disease are particularly high. Despite progress in understanding of the mutational and expression landscape associated with OSCC, advances in deciphering these alterations for the development of therapeutic strategies have been limited. Further insight into the molecular cues that contribute to OSCC is therefore required. Here we show that the transcriptional regulators YAP (YAP1) and TAZ (WWTR1), which are key effectors of the Hippo pathway, drive pro-tumorigenic signals in OSCC. Regions of pre-malignant oral tissues exhibit aberrant nuclear YAP accumulation, suggesting that dysregulated YAP activity contributes to the onset of OSCC. Supporting this premise, we determined that nuclear YAP and TAZ activity drives OSCC cell proliferation, survival, and migration in vitro, and is required for OSCC tumor growth and metastasis in vivo. Global gene expression profiles associated with YAP and TAZ knockdown revealed changes in the control of gene expression implicated in pro-tumorigenic signaling, including those required for cell cycle progression and survival. Notably, the transcriptional signature regulated by YAP and TAZ significantly correlates with gene expression changes occurring in human OSCCs identified by The Cancer Genome Atlas (TCGA), emphasizing a central role for YAP and TAZ in OSCC biology. Expression profiling was conducted following the repression of the transcriptional regulators TAZ and YAP (YAP/TAZ) in human SCC2 oral cancer cells. Human SCC2 oral cancer cells were transfected with control siRNA, or siRNAs targeting TAZ, YAP, or YAP/TAZ for 48 hours. Total RNA from three independent experiments carried out on separate days was isolated and purified and the samples were then profiled on Affymetrix Human Gene 2.0 Chips at the Boston University Microarray Core. The expression profiles were processed and normalized using the Robust Multi-array Average (RMA) procedure (23) based on a custom Brainarray CDF (24). For each of the siRNA experiments, signatures of genes differentially expressed between treatment and corresponding siRNA control with an FDR q-value ?0.05 and a fold change ?2 were identified as either activated (up-regulated in control) or repressed (up-regulated in treatment). The overlap between the differentially expressed gene signatures was evaluated by Fisher test. Hierarchical gene and sample clustering was performed on the top 3000 genes with highest median absolute deviation (MAD; a robust version of the variance) across 12 samples, using “ward” as the agglomeration rule, and 1 minus Pearson correlation and Euclidean as the distance measures for genes and samples, respectively.
2015-05-26 | E-GEOD-66949 | biostudies-arrayexpress
Project description:Oral squamous cell carcinoma (OSCC) is a main reason of oral cancer mortality and morbidity. Cancer of oral cavity in central south Asia, ranks among third most common kinds of cancer. The discovery of candidate markers to differentiate normal from malignant cells in clinical diagnosis of OSCC would be of critical importance because this malignancy has poor prognosis. To improve the clinical outcome in OSCC patients, the present study was aimed at identifying robust candidate biomarkers for early OSCC diagnosis and to enhance understanding of the mechanisms of disease progression and pathogenesis. Of particular interest are proteins that can be found in tissue lysates of OSCC tumor vs normal adjacent mucosa samples and secreted in cell line Secretomes of HNSCC for non-invasive detection. We analysed 17 paired human malignant OSCC tissues and normal adjacent tissue in addition to secretomes of 9 HNSCC cell lines. The proteome dataset of OSCC and normal tissues consisted of 5,123 protein groups, including 299 proteins with strong differential expression (p-value <0.01, fold change barrier to ˃+2 and <-2, 205 upregulated and 94 down regulated) and 134 common proteins were also found out of total dataset of 4473 identified proteins of HNSCC cell line secretomes. Functional data analysis revealed that these differential proteins were significantly associated with multiple biological processes. Myogenesis, Fatty Acid Metabolism and KRAS Signaling DN were associated with the proteins downregulated in cancer tissues, while Protein Secretion, Unfolded Protein Response, Spliceosomal complex assembly, Protein localization to endosome and Interferon Gamma Response were enriched in the set of upregulated proteins and these regulated proteins may be classically or non-classically secreted. Furthermore, we found differential enrichment of Creb3L1, ESRRA, YY, ELF2, STAT1 and XBP transcription factors potentially regulating these major pathways.
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Project description:Oral squamous cell carcinoma (OSCC) shows high mortality rates that are largely associated with the presence of lymph node metastasis. However, the molecular mechanisms that drive OSCC metastasis are unknown. Here, we used a reductionist approach mapping the proteomic, miRNA, metabolomic and lipidomic profiles of extracellular vesicles (EVs) from human primary tumor (SCC-9 cells) and matched lymph node metastasis (LN1 cells) to explore the role of EV cargo in OSCC metastasis. Distinct omics profiles were associated with the metastatic phenotype, including 670 proteins, 217 miRNAs, 26 metabolites and 64 lipids differentially abundant between LN1 and SCC-9-derived EVs. A multi-omics integration indicated 11 ‘hub proteins’ significantly modulated in the metastatic site when compared to primary site-derived EVs, seven of them correlated with aggressiveness in cancer patients. The multi-omics approach allowed the prospection of proteins transported by EVs that potentially serves as prognostic markers in OSCC.
2021-07-19 | PXD019216 | Pride
Project description:The purpose of this study was to provide molecular evidence that surgical margin definition using narrow band imaging (NBI) resulted in more complete OSCC excision that conventional while light (WL) imaging. Samples were taken prospectively from 18 patients undergoing surgical resection for intraoral SCC (excluding lip, pharynx and hypopharynx). Biopsies were taken from the tumour and from 5mm beyond each of the abnormal tissue margins defined by WL and NBI. Transcriptional profiling was performed by microarray.
2018-01-17 | E-MTAB-5933 | biostudies-arrayexpress
Project description:The purpose of this study was to provide molecular evidence that surgical margin definition using narrow band imaging (NBI) resulted in more complete OSCC excision that conventional while light (WL) imaging. Samples were taken prospectively from 18 patients undergoing surgical resection for intraoral SCC (excluding lip, pharynx and hypopharynx). Biopsies were taken from the tumour and from 5mm beyond each of the abnormal tissue margins defined by WL and NBI. MicroRNA profiling was performed by microarray.
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