Abstract

Plant-derived nanoparticles exert cytoprotective effects on intestinal cells by delivering their cargo to intestinal tissues. We previously reported that apple-derived nanoparticles (APNPs) downregulate themRNA of the human intestinal transporterOATP2B1/SLCO2B1and that the 3'UTR region is required for the response to APNPs. Here, we investigated the involvement of microRNAs (miRNAs) in APNPs in suppressing OATP2B1 expression to demonstrate that APNP macromolecules directly interact with intestinal tissues. Using in silicoanalysis, seven apple miRNAs were predicted as candidate miRNAs that interact with theSLCO2B1-3'UTR. The APNP-mediated decrease in luciferase activity of pGL3/SLCO2B1-3'UTR was abrogated by inhibitors of mdm-miR-160a-e, -7121a-c, or -7121d-h. Each miRNA mimicreduced the endogenous expression of SLCO2B1mRNA in Caco-2 cells. The luciferase activity of thetruncated pGL3/SLCO2B1-3'UTR, whichcontains approximately 200 bp around each miRNA recognition element (MRE), was decreased by the miR-7121d-h mimic but little by the other mimics. APNP also reduced the luciferase activity of truncated pGL3/SLCO2B1-3'UTR containing an MRE for miR-7121d-h. Thus, we demonstrated that mdm-miR-7121d-h contributes to the APNP-mediated downregulation of intestinal OATP2B1. Accordingly, plant macromolecules, such as miRNAs, may directly interact with intestinal tissues viananoparticles.

Significance Statement We demonstrated that mdm-miR7121d-h contained in apple-derived nanoparticles downregulated the mRNA expression of SLCO2B1by interacting with SLCO2B1-3’UTR directly and that SLCO2B1mRNA might also be decreased by mdm-miR160a-e and -7121a-c indirectly. This finding that the specific apple-derived miRNAs influence human intestinal transporters provides a novel concept that macromolecules in foods directly interact and affect the intestinal function of the host.