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Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia

ABSTRACT: Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia

PROVIDER: PRJNA430693 | ENA |

REPOSITORIES: ENA

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Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia

Project description:In tumor tissues, hypoxia is a commonly observed feature resulting from rapidly proliferating cancer cells outgrowing the surrounding vasculature network. The four-step isogenic BJ cell model enables studies of defined steps of tumorigenesis: the normal, immortalized, transformed, and metastasizing stages. By transcriptome profiling under atmospheric and moderate hypoxic (3% O2) conditions, we observed that despite being highly similar, the four cell lines responded strikingly different to hypoxia. We demonstrate that the transcriptome adaptation to moderate hypoxia resembles the process of malignant transformation. The transformed cells displayed a distinct capability of metabolic switching, reflected in reversed gene expression patterns for several genes involved in oxidative phosphorylation and glycolytic pathways. By profiling the stage-specific responses to hypoxia, we identified ASS1 as a potential prognostic marker in hypoxic tumors. This study demonstrates the usefulness of the BJ cell model for highlighting the interconnection of pathways involved in malignant transformation and hypoxic response.

2018-05-09 | GSE109367 | GEO

Downregulation of WDR20 due to loss of 14q is involved in the malignant transformation of clear cell renal cell carcinoma

Project description:Previously, we have reported that genomic loss of 14q occurs more frequently in high grade clear cell renal cell carcinomas (ccRCCs) than low grade ones and shows a significant impact on the expression levels of genes located on this region, suggesting that the genes located on the region and downregulated by the loss may be involved in the malignant transformation of ccRCCs. Here, among the genes located on the minimal common region of 14q loss, we found that 6 were significantly downregulated in high grade ccRCCs due to copy number loss. Using the data set from The Cancer Genome Atlas (TCGA) Research Network, downregulation of one out of the 6 genes, WDR20, was significantly associated with poorer prognosis for the patients with ccRCC, suggesting that downregulation of WDR20 may be involved in the malignant transformation of ccRCC. In functional assays, exogeneous WDR20 significantly inhibited growth and induced apoptosis in RCC cell lines. Interestingly, the phosphorylation levels of ERK and AKT, which reportedly contribute to the malignant phenotype of RCC cells, were clearly reduced by the exogeneous expression of WDR20. Thus, our data suggest that downregulation of WDR20 due to 14q loss may be involved in the malignant transformation of ccRCCs in part through the activation of ERK and AKT pathways.

2016-08-09 | GSE71963 | GEO

Downregulation of WDR20 due to loss of 14q is involved in the malignant transformation of clear cell renal cell carcinoma

2016-08-09 | E-GEOD-71963 | biostudies-arrayexpress

Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia.

Project description: Not available

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Patterns of aberrant DNA methylation after toxicant-induced malignant transformation

Project description:This SuperSeries is composed of the following subset Series: GSE38926: Patterns of aberrant DNA methylation after toxicant-induced malignant transformation (MeDIP-chip dataset 1) GSE38928: Patterns of aberrant DNA methylation after toxicant-induced malignant transformation (MeDIP-chip dataset 2) GSE38929: Patterns of aberrant DNA methylation after toxicant-induced malignant transformation (miRNA dataset) Refer to individual Series

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Gene expression changes associated with malignant transformation of oral potentially malignant disorders

Project description:A large number of oral squamous cell carcinomas (OSCCs) are believed to be preceded by oral potentially malignant disorders (OPMD) that have an increased likelihood of malignant transformation compared to clinically normal mucosa. This study was performed to identify differentially expressed genes between OPMDs that underwent malignant transformation (MT) and those that did not, termed ‘non-transforming’ (NT) cases. Total RNA was extracted from formalin-fixed paraffin-embedded tissue biopsies of 20 OPMD cases with known clinical outcomes (10 MT vs. 10 NT). Samples were assessed for quantity, quality and integrity of RNA prior to sequencing. Analysis for differential gene expression between MT and NT was performed using statistical packages in R. Genes were considered to be significantly differentially expressed if the False Discovery Rate corrected p-value was < 0.05. RNA yield was variable but RNA purity was good (A260/A280 >1.90). Analysis of RNA-Sequencing outputs revealed 41 genes (34 protein-coding; 7 non-coding) that were significantly differentially expressed between MT and NT cases. The log2 fold change for the statistically significant differentially expressed genes ranged from -2.63 to 2.48, with 23 protein-coding genes being downregulated and 11 protein-coding genes being upregulated in MT cases compared to NT cases. Several candidate genes that may play a role in malignant transformation of OPMD have been identified. Experiments to validate these candidates are underway. It is anticipated that this work will contribute to better understanding of the aetiopathogenesis of OPMD and development of novel biomarkers.

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DNA methylation and hydroxymethylation mediated gene expression regulation network involved in 3-methylcholanthrene induced lung cell malignant transformation

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