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Circulating plant miRNAs can regulate human gene expression in vitro

View Article: PubMed Central - PubMed

ABSTRACT

While Brassica oleracea vegetables have been linked to cancer prevention, the exact mechanism remains unknown. Regulation of gene expression by cross-species microRNAs has been previously reported; however, its link to cancer suppression remains unexplored. In this study we address both issues. We confirm plant microRNAs in human blood in a large nutrigenomics study cohort and in a randomized dose-controlled trial, finding a significant positive correlation between the daily amount of broccoli consumed and the amount of microRNA in the blood. We also demonstrate that Brassica microRNAs regulate expression of human genes and proteins in vitro, and that microRNAs cooperate with other Brassica-specific compounds in a possible cancer-preventive mechanism. Combined, we provide strong evidence and a possible multimodal mechanism for broccoli in cancer prevention.

No MeSH data available.


Related in: MedlinePlus

Heatmap of deregulated genes in gastric biopsies or gastric cancer cell line.The figure shows fold change for 11 genes and miR160 in 5 set of samples. High glucosinolate (HG) and regular represent samples from gastric biopsies after ingestion of HG (enriched in sulforaphane) or regular broccoli as per Gasper et al.22, and fold change data is collected from the same paper. Sulforaphane, DIM and miR160 refer to MNK45 cell line treated with each of the named molecules, and fold change was measured by real time PCR (log transformed to be comparable to Gasper et al. fold change). Blue blocks represent downregulated genes, red to green blocks upregulated ones. Grey blocks are missing values from Gasper et al. paper.
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f4: Heatmap of deregulated genes in gastric biopsies or gastric cancer cell line.The figure shows fold change for 11 genes and miR160 in 5 set of samples. High glucosinolate (HG) and regular represent samples from gastric biopsies after ingestion of HG (enriched in sulforaphane) or regular broccoli as per Gasper et al.22, and fold change data is collected from the same paper. Sulforaphane, DIM and miR160 refer to MNK45 cell line treated with each of the named molecules, and fold change was measured by real time PCR (log transformed to be comparable to Gasper et al. fold change). Blue blocks represent downregulated genes, red to green blocks upregulated ones. Grey blocks are missing values from Gasper et al. paper.

Mentions: We decided to test 11 genes, 4 deregulated after HG broccoli exposure, 3 deregulated after regular broccoli exposure and 4 in common between the two sets, in a gastric cell line expressing all these targets, MNK45. We transfected the cells with miR160 mimic, and treated them with sulforaphane or DIM, and for each treatment, we tested the change in expression of the selected genes. DIM was included in the experiment because it is one of the two isothiocyanates present in Brassicaceae, together with sulforaphane, most frequently studied for their anticancer properties10. As shown in Fig. 4, the two genes upregulated in HG gastric biopsies are also upregulated after treatment with sulforaphane while only one (AKR1C2) is upregulated after treatment with DIM. Of the remaining 9 downregulated genes, 6 were deregulated solely by miR160, one by miR160 and sulforaphane (DUSP4) and one by miR160 and DIM (FOS). Student’s t test p-values calculated for each gene in DIM, sulforaphane or miR160 treatment against not treated cell lines are listed in Supplementary Table 7.


Circulating plant miRNAs can regulate human gene expression in vitro
Heatmap of deregulated genes in gastric biopsies or gastric cancer cell line.The figure shows fold change for 11 genes and miR160 in 5 set of samples. High glucosinolate (HG) and regular represent samples from gastric biopsies after ingestion of HG (enriched in sulforaphane) or regular broccoli as per Gasper et al.22, and fold change data is collected from the same paper. Sulforaphane, DIM and miR160 refer to MNK45 cell line treated with each of the named molecules, and fold change was measured by real time PCR (log transformed to be comparable to Gasper et al. fold change). Blue blocks represent downregulated genes, red to green blocks upregulated ones. Grey blocks are missing values from Gasper et al. paper.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5015063&req=5

f4: Heatmap of deregulated genes in gastric biopsies or gastric cancer cell line.The figure shows fold change for 11 genes and miR160 in 5 set of samples. High glucosinolate (HG) and regular represent samples from gastric biopsies after ingestion of HG (enriched in sulforaphane) or regular broccoli as per Gasper et al.22, and fold change data is collected from the same paper. Sulforaphane, DIM and miR160 refer to MNK45 cell line treated with each of the named molecules, and fold change was measured by real time PCR (log transformed to be comparable to Gasper et al. fold change). Blue blocks represent downregulated genes, red to green blocks upregulated ones. Grey blocks are missing values from Gasper et al. paper.
Mentions: We decided to test 11 genes, 4 deregulated after HG broccoli exposure, 3 deregulated after regular broccoli exposure and 4 in common between the two sets, in a gastric cell line expressing all these targets, MNK45. We transfected the cells with miR160 mimic, and treated them with sulforaphane or DIM, and for each treatment, we tested the change in expression of the selected genes. DIM was included in the experiment because it is one of the two isothiocyanates present in Brassicaceae, together with sulforaphane, most frequently studied for their anticancer properties10. As shown in Fig. 4, the two genes upregulated in HG gastric biopsies are also upregulated after treatment with sulforaphane while only one (AKR1C2) is upregulated after treatment with DIM. Of the remaining 9 downregulated genes, 6 were deregulated solely by miR160, one by miR160 and sulforaphane (DUSP4) and one by miR160 and DIM (FOS). Student’s t test p-values calculated for each gene in DIM, sulforaphane or miR160 treatment against not treated cell lines are listed in Supplementary Table 7.

View Article: PubMed Central - PubMed

ABSTRACT

While Brassica oleracea vegetables have been linked to cancer prevention, the exact mechanism remains unknown. Regulation of gene expression by cross-species microRNAs has been previously reported; however, its link to cancer suppression remains unexplored. In this study we address both issues. We confirm plant microRNAs in human blood in a large nutrigenomics study cohort and in a randomized dose-controlled trial, finding a significant positive correlation between the daily amount of broccoli consumed and the amount of microRNA in the blood. We also demonstrate that Brassica microRNAs regulate expression of human genes and proteins in vitro, and that microRNAs cooperate with other Brassica-specific compounds in a possible cancer-preventive mechanism. Combined, we provide strong evidence and a possible multimodal mechanism for broccoli in cancer prevention.

No MeSH data available.


Related in: MedlinePlus