Mechanistic insights into anti-cancer properties of oligomeric proanthocyanidins from grape seeds in colorectal cancer
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ABSTRACT:
PROVIDER: PRJNA431467 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6509700.fastq.gz | Fastqsanger.gz | |||
| SRR6509710.fastq.gz | Fastqsanger.gz | |||
| SRR6509720.fastq.gz | Fastqsanger.gz | |||
| SRR6509701.fastq.gz | Fastqsanger.gz | |||
| SRR6509711.fastq.gz | Fastqsanger.gz |
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Project description:Although the anti-cancer properties of Oligomeric Proanthocyanidins (OPCs) from grape seeds has been well recognized, the molecular mechanisms by which they exert anti-cancer effects are poorly understood. In this study, through comprehensive RNA-sequencing based gene-expression profiling in multiple colorectal cancer cell lines, we for the first time illuminate the genome-wide effects of OPCs from grape seeds in colorectal cancer. Our data revealed that OPCs affects several key cancer-associated genes. In particular, genes involved in cell cycle and DNA replication were most significantly and consistently altered by OPCs across multiple cell lines. Intriguingly, our in vivo experiments showed that OPCs was significantly more potent at decreasing xenograft tumor growth compared to the unfractionated grape seed extract (GSE) that includes the larger polymers of proanthocyanidins. These findings were further confirmed in colorectal cancer patient-derived organoids, wherein OPCs more potently inhibited the formation of organoids compared to GSE. Further, we validated alteration of cell cycle and DNA replication associated genes in cancer cell lines, mice xenografts as well as patient-derived organoids. Overall, this study provides an unbiased and comprehensive look at the mechanisms by which OPCs exerts anti-cancer properties in colorectal cancer.
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Project description:Mi(cro)RNAs are small non-coding RNAs of 18-25 nucleotides in length that modulate gene expression at the posttranscriptional level. Grape seed proanthocyanidins (GSPs), a biologically active component of grape seeds, have been shown to have positive effects on anti-cancer. In current study, to explore whether GSPs can regulate miRNA expression and possible molecular mechanisms involved in anti-cancer, we prepared the pancreatic cancer (PC) cells samples (SS3, SS12 and SS24) at 3, 12 and 24h after GSPs treatments respectively; and control samples (SC3, SC12 and SC24) were also collected accordingly. miRNA-seq transcriptome comparisons were performed, and 26, 85 and 85 differentially expressed (DE) miRNA were identified among SS3 vs. SC3, SS12 vs. SC12 and SS24 vs. SC24 respectively, indicating the GSPs treatments could modulate the expression of miRNAs globally. Subsequently, 74, 598 and 1204 target genes of these DE miRNAs were predicted in three comparisons, and GO and KEGG analysis revealed that multiple target genes were associated with proliferation and apoptosis of PC cells. Moreover, interaction network analyis of DE miRNAs and target genes associated with PC were also carried out, and fabulous co-expression relationships further suggested that GSPs treatment could probably repress the proliferation of PC cells by modulating the miRNAs expression
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Project description:Grape Proanthocyanidins Modulate MicroRNA Expression in Human pancreatic cancer cells
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Project description:Although the anticancer properties of oligomeric proanthocyanidins (OPCs) from grape seeds have been well recognized, the molecular mechanisms by which they exert anticancer effects are poorly understood. In this study, through comprehensive RNA-sequencing-based gene expression profiling in multiple colorectal cancer cell lines, we for the first time illuminate the genome-wide effects of OPCs from grape seeds in colorectal cancer. Our data revealed that OPCs affect several key cancer-associated genes. In particular, genes involved in cell cycle and DNA replication were most significantly and consistently altered by OPCs across multiple cell lines. Intriguingly, our in vivo experiments showed that OPCs were significantly more potent at decreasing xenograft tumor growth compared with the unfractionated grape seed extract (GSE) that includes the larger polymers of proanthocyanidins. These findings were further confirmed in colorectal cancer patient-derived organoids, wherein OPCs more potently inhibited the formation of organoids compared with GSE. Furthermore, we validated alteration of cell cycle and DNA replication-associated genes in cancer cell lines, mice xenografts as well as patient-derived organoids. Overall, this study provides an unbiased and comprehensive look at the mechanisms by which OPCs exert anticancer properties in colorectal cancer.
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Project description:Mi(cro)RNAs are small non-coding RNAs of 18-25 nucleotides in length that modulate gene expression at the post-transcriptional level. These RNAs have been shown to be involved in a several biological processes, human diseases and metabolic disorders. Proanthocyanidins, which are the most abundant polyphenol class in the human diet, have positive heath effects on a variety of metabolic disorders such as inflammation, obesity, diabetes and insulin resistance. The present study aimed to evaluate whether proanthocyanidin-rich natural extracts modulate miRNA expression. Using microarray analysis and Q-PCR, we investigated miRNA expression in HepG2 cells treated with proanthocyanidins. Our results showed that when HepG2 cells were treated with grape seed proanthocyanidin extract (GSPE), cocoa proanthocyanidin extract (CPE) or pure epigallocatechin gallate isolated from green tea (EGCG), fifteen, six and five differentially expressed miRNAs, respectively, were identified out of 904 mRNAs. Specifically, miR-30b* was downregulated by the three treatments, and treatment with GSPE or CPE upregulated miR-1224-3p, miR-197 and miR-532-3p. Therefore, these results provide evidence of the capacity of dietary proanthocyanidins to influence microRNA expression, revealing a new mechanism of action of proanthocyanidins. microRNA profiling of Human hepatocellular liver carcinoma cell line (HepG2) comparing control untreated HepG2 cells with cells treated with grape seed proanthocyanidin extract (100 mg/L, 5h), cacao proanthocyanidin extract (100 mg/L, 5h) or epigallocatechin gallate (50 mg/L, 5h). Two biologival replicates were used for control and treated cells with one replicate per array.
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Project description:Mi(cro)RNAs are small non-coding RNAs of 18-25 nucleotides in length that modulate gene expression at the post-transcriptional level. These RNAs have been shown to be involved in a several biological processes, human diseases and metabolic disorders. Proanthocyanidins, which are the most abundant polyphenol class in the human diet, have positive heath effects on a variety of metabolic disorders such as inflammation, obesity, diabetes and insulin resistance. The present study aimed to evaluate whether proanthocyanidin-rich natural extracts modulate miRNA expression. Using microarray analysis and Q-PCR, we investigated miRNA expression in HepG2 cells treated with proanthocyanidins. Our results showed that when HepG2 cells were treated with grape seed proanthocyanidin extract (GSPE), cocoa proanthocyanidin extract (CPE) or pure epigallocatechin gallate isolated from green tea (EGCG), fifteen, six and five differentially expressed miRNAs, respectively, were identified out of 904 mRNAs. Specifically, miR-30b* was downregulated by the three treatments, and treatment with GSPE or CPE upregulated miR-1224-3p, miR-197 and miR-532-3p. Therefore, these results provide evidence of the capacity of dietary proanthocyanidins to influence microRNA expression, revealing a new mechanism of action of proanthocyanidins.
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