MicroRNAs (miRNAs), a class of single-stranded non-coding RNA of about 22 nucleotides, are potent regulators of gene expression existing in both plants and animals. Recent studies showed that plant miRNAs could enter mammalian bloodstream via gastrointestinal tract, through which access a variety of tissues and cells of recipients to exert therapeutic effects. This intriguing phenomenon indicates that miRNAs of diet/plant origin may act as a new class of bioactive ingredients communicating with mammalian systems. In this review, in order to pinpoint the reason underlying discrepancies of miRNAs transmission from diet/plant to animals, the pathways that generate miRNAs and machineries involved in the functions of miRNAs in both kingdoms were outlined and compared. Then, the current controversies concerning cross-kingdom regulations and the potential mechanisms responsible for absorption and transfer of diet/plant-derived miRNAs were interpreted. Furthermore, the hormone-like action of miRNAs and the intricate interplay between miRNAs and hormones were implicated. Finally, how these findings may impact nutrition and medicine were briefly discussed.

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