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Effect of Okadaic Acid on gene expression in human pancreatic cells

ABSTRACT: Effect of Okadaic Acid on gene expression in human pancreatic cells

PROVIDER: PRJNA891748 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21954067.fastq.gz	Fastqsanger.gz
	SRR21954068.fastq.gz	Fastqsanger.gz
	SRR21954069.fastq.gz	Fastqsanger.gz
	SRR21954070.fastq.gz	Fastqsanger.gz
	SRR21954071.fastq.gz	Fastqsanger.gz

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Effect of Okadaic Acid on gene expression in human pancreatic cells

Project description:Pancreatic ductal adenocarcinoma (PDAC) has a bad prognosis, a fast progression and is difficult to treat, highlighting the need for new therapeutic targets. Aggressive tumors mostly show Epithelial-to-Mesenchymal Transition (EMT). Protein phosphatase type 2A (PP2A) plays a central role in processes of cell survival and proliferation, but the link with EMT and tumor progression is largely unknown. Therefore, we examined expression of a PP2A gene set in five datasets of human PDAC and their association with an aggressive phenotype. Two datasets included PDAC tumor samples and normal pancreatic tissue. In two other datasets, the samples could be classified into clinical/molecular subtypes of EMT-high/aggressive and EMT-low/moderate PDAC. Spearman correlation, hierarchical clustering and ROC-analysis were performed. EMT was also quantified using weighted expression of 8 marker genes. In each study we observed that, compared to normal tissue, (advanced) tumor stage positively and significantly correlated with EMT. EMT-high PDAC showed suppression of PPP2R1B and PPP2R2D expression and upregulation of PPP2R3C, PPP2R5E, STRN, STRN3 and PPP2R2A. A strong link was further found for upregulation of endogenous inhibitors of PP2A (KIAA1524/CIP2A, ARPP19, TIPRL and PPME1) with advanced PDAC. ROC-curve indicates that high expression of PP2A-inhibitors are predictors of aggressive PDAC. This was further investigated in a cell line model of Panc-1 cells made resistant to the PP2A-inhibitor Okadaic acid. Gene expression was determined in cells exposed for 24 hours and resistant cells. In summary, we demonstrate an important association of PP2A inhibition with EMT in advanced human pancreatic cancer. We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different cells.

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