Inter-kingdom regulation of human transcriptome by dietary microRNAs: Emerging bioactives from edible plants to treat human diseases?

ABSTRACT

Abstract Background MicroRNAs (miRNAs) are small non-coding RNAs between 18 and 23 nts in size which regulate the translation and stability of target mRNAs. MiRNAs from dietary plants are conventionally thought to be degraded during the gastrointestinal digestion process. A few recent reports suggest that dietary microRNAs may exhibit resistance to this process, enter systemic circulation and exert biological effects on animal physiology. Scope and approach The horizontal transfer of miRNAs into systemic circulation is not feasible for all dietary miRNAs due to lack of bioavailability. Hence, this is a highly debated proposition with conflicting data presented in literature. Dietary miRNAs may exhibit such cross-kingdom regulation if present in extracellular vesicles which increases their bioavailability. These vesicular structures from plants are known as edible nanoparticles (ENPs). ENPs have been isolated from several edible plants. These nano-sized vesicles are filled with bioactives, proteins, lipids and miRNAs, in a bioavailable form. ENP-derived miRNAs are gaining attention due to their relative stability and resistance to degradation. ENP-derived miRNAs may enter systemic circulation and target mRNAs in recipient cells. With the COVID-19 pandemic threat worldwide, it appears that ENP-derived miRNAs could also be exploited for targeted therapeutics against SARS-CoV-2. Key findings and conclusions ENP-derived miRNAs are probably more bioavailable and are spontaneously absorbed in intestinal epithelium to suppress target transcripts in human/microbial/viral kingdoms. Such cross-kingdom regulation exhibited by dietary miRNAs, if properly investigated and validated, may aid in the development of non-toxic and cost-effective therapeutics to treat human diseases.