Identification of the Micro‐Ribonucleic Acid Profiles of Plant‐Derived Extracellular Vesicles and their Potential Crosskingdom Regulation

Plant‐derived extracellular vesicles (pEVs) are nanosized vesicles that have comparable structure and properties to EVs derived from mammalian cells. Prior studies have confirmed that pEVs have remarkable efficacy in the treatment of human diseases, such as cancer. As critical regulators of gene expression, microRNAs (miRNAs) are abundant in pEVs. However, their potential functional roles and regulatory mechanisms in mediating crosskingdom regulation of mammalian cells by pEVs remain undefined. In particular, the similarities and differences in the miRNA profiles of various pEVs in gene regulation remain elusive. Herein, pEVs are isolated from grapefruit, ginger, lemon, and grape, and small RNA (sRNA) libraries are constructed to perform sRNA sequencing. Only 15 consistently expressed miRNAs are identified in these pEVs. Furthermore, the top 20 miRNAs of each pEV are highly expressed among total miRNAs, accounting for 79.93–87.12%. Through functional annotation analysis of the miRNA target genes, these miRNAs are found to be involved in regulating the progression of human cancer and viral infection. Taken together, this study demonstrates that the miRNAs contained in the pEVs play a critical role in mediating the potential crosskingdom regulatory effects against human genes and highlights their significant potential therapeutic applications in human diseases.