Dietary plant microRNAs as potential regulators of cellular cholesterol efflux.

Epidemiological evidence suggests adherence to vegetable-rich diets is associated to atheroprotective effects and bioactive components are most likely to play a relevant role. The notion of inter-kingdom regulation has opened a new research paradigm and perhaps microRNAs (miRNAs) from edible vegetables could influence consumer gene expression and lead to biological effects. We aimed to investigate the potential impact of broccoli-derived miRNAs on cellular cholesterol efflux in vitro. Four miRNAs (miR159a, miR159b, miR166a and miR403) from Brassica oleracea var. italica (broccoli), a widely consumed cruciferous vegetable, were selected for further investigation, based on their high abundancy in this vegetable and their presence in other plants. Selected miRNAs were synthesized with a 3'-terminal 2'-O-methylation and their cellular toxicity, in vitro gastrointestinal resistance and cellular uptake were evaluated. Potential target genes within the mammalian transcriptome were assessed in silico following pathway analysis. In vitro cholesterol efflux was assessed in human THP-1-derived macrophages. miRNAs survival to in vitro GI digestion was around 1%, although some variation was seen between the four candidates. Cellular uptake by mammalian cells was confirmed, and an increase in cholesterol efflux was observed. Pathway analysis suggested these miRNAs are involved in biological processes related to phosphorylation, phosphatidylinositol and Wnt signaling, and to the insulin/IGF pathway. Health-promoting properties attributed to cruciferous vegetables, might be mediated (at least in part) through miRNA-related mechanisms.

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