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Transcriptome-wide in vitro effects of aspirin on patient-derived normal colon organoids

ABSTRACT: Transcriptome-wide in vitro effects of aspirin on patient-derived normal colon organoids

PROVIDER: PRJNA685544 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13257800_1.fastq.gz	Fastqsanger.gz
	SRR13257800_2.fastq.gz	Fastqsanger.gz
	SRR13257801_1.fastq.gz	Fastqsanger.gz
	SRR13257801_2.fastq.gz	Fastqsanger.gz
	SRR13257802_1.fastq.gz	Fastqsanger.gz

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Transcriptome-wide in vitro effects of aspirin on patient-derived normal colon organoids

Project description:Here, we used bulk RNA-seq data derived from healthy colon organoids (un)exposed to aspirin. Through the use of external single cell RNA-seq data, we estimate changes in cell composition. We extend this analysis by controlling for cell composition and performing WGCNA to identify modules of co-expression differentially affected by aspirin treatment in colon organoids.

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Project description:Temporal analysis of colon carcinoma cell line CC531 response to 4.5 mM butyrate or 3 mM aspirin. Samples taken at 2, 6, 12, 16 and 24 hours. The CC531 cell line has been widely used to study different aspects of tumor growth and metastasis and provides an excellent experimental platform to develop novel antitumor strategies. To characterize the CC531 model at the molecular level, we screened for mutations in genes covering important signal-transduction pathways that are known to play major roles during colon carcinogenesis, the wnt and the ki-ras signaling pathways. We found both a prototypic beta-catenin (Ctnnb1) mutation (Thr(41)Ile) and a ki-ras (G12D) mutation, providing unambiguous evidence for the constitutive activation of these pathways in CC531 cells. We further established comprehensive gene expression profiles of CC531 cells and investigated the molecular response to 2 antitumor drugs, butyrate and aspirin. Using oligonucleotide microarrays, we screened the expression levels of 7,700 genes and identified a total of 398 genes whose expression was significantly changed upon treatment with butyrate. When using aspirin, 121 genes were significantly altered. Interestingly, 36 genes were regulated by both butyrate and aspirin and 35 of them were regulated in the same direction. We found 7 differentially expressed genes, cyclin D1, cyclin E, c-myc, Fosl1, c-fos, Cd44 and follistatin, which are known targets of the beta-catenin and/or the ras pathway. In all cases, butyrate and aspirin reversed the changes in expression normally found in response to active signaling of these oncogenic pathways. Keywords: other

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