Effects of different forms of Anthocyanins on growth inhibition and gene expression of CRC cells
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ABSTRACT:
PROVIDER: PRJNA1014006 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25945260_1.fastq.gz | Fastqsanger.gz | |||
| SRR25945260_2.fastq.gz | Fastqsanger.gz | |||
| SRR25945261_1.fastq.gz | Fastqsanger.gz | |||
| SRR25945261_2.fastq.gz | Fastqsanger.gz | |||
| SRR25945262_1.fastq.gz | Fastqsanger.gz |
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Project description:Scope: Anthocyanins from diet were found to have therapeutic potential for various cancers including colorectal cancer (CRC). Given the diverse forms of anthocyanins, it is unclear whether different types of anthocyanins share common pathways in regulating intestinal cell function. This study aims to investigate the core gene pathways modulated by anthocyanins in intestinal cells, and to identify potential compounds with similar therapeutic effects.Methods and results: Three different forms anthocyanins were used to treat CRC cells at different concentrations and time points, and growth inhibition was observed in all anthocyanins, with varying patterns. RNA-seq analysis showed that the regulatory-pathways of anthocyanins with different structures were different, and the time factor had a greater effect. Time-series analysis of regulatory-genes shared by different concentrations and structures of anthocyanins was performed. By overlapping with public PPAR target gene set, a core gene set across three types of anthocyanins was identified and used in Connectivity Map (CMap) analysis to screen for compounds. The repositioned drug candidates included known anti-cancer drugs that have effects of transcriptome interventions similar to anthocyanins.Conclusion: These findings provide new insights into the mechanisms underlying the anti-CRC effects of anthocyanins and may facilitate the development of novel therapeutic agents for CRC.
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Project description:A collection of genetically engineered mouse models (GEMM) of colorectal cancer (CRC) were created, and primary tumors from these GEMMs were analyzed. Primary CRC tumors from these GEMMs were genotyped to confirm that they contain the core genetic lesions of interest, including APC, P53, KRAS, and BRAF. Primary tumors from GEMMs with combinations of lesions of interest were analyzed by whole genome expression, and their expression profiles were compared to determine how they segregate. Signatures were then generated from GEMM tumors of interest and compared to human clinical datasets with expression and outcome data. Primary tumors from CRC GEMMs with different combinations of mutant alleles of interested were generated and analyzed. Alleles include mutant forms of APC (A), P53 (P), KRAS (K) and BRAF (B).
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Project description:Interventions: Group 1: Arm 1 - 0.33 L Anthocyanin-rich blueberry / grape juice daily for 28 days. This is followed by a wash-out period of 10 days and a run-in phase of 7 days.
Group 2: Arm 1 - 0.33 L Anthocyanin-reduced blueberry / grape juice daily for 28 days. This is followed by a wash-out period of 10 days and a run-in phase of 7 days.
Primary outcome(s): Inhibition of tumor cell migration in vitro after application of plasma-isolated anthocyanins and metabolites. The endpoint is recorded after 28 days compared to day 1.
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Project description:Anthocyanins are high value plant antioxidants which are not present in the fruits of cultivated tomato. However, both the dominant gene Anthocyanin fruit (Aft) and the recessive gene atroviolacea (atv), introgressed into domesticated tomato from two different wild Solanum species, stimulate a limited anthocyanin pigmentation. Surprisingly, double mutant Aft/Aft atv/atv tomatoes are characterised by the presence of anthocyanins in the fruit peel, resulting in intensely purple pigmented fruit. We carried out a transcript profiling analysis using GeneChip® Tomato Genome Arrays, in order to identify differentially expressed genes when comparing wild type, Aft/Aft, atv/atv, and Aft/Aft atv/atv fruits. The expression pattern of several genes involved in the anthocyanin pathway was analyzed in detail. Among the fruit peel-associated differentially expressed transcripts, genes involved in phenylpropanoid pathway, cell wall composition, biotic and abiotic stress responses, sugar and hormone metabolism were overrepresented in Aft/Aft atv/atv. Transcriptomic analysis thus revealed that the activation of anthocyanin synthesis in tomato fruit was accompanied by a complex remodulation of gene expression, likely affecting important agronomic and merceological traits.
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