Integrated analysis of enzymes, mRNAs, and miRNAs provides insight into the regulatory potential of extracellular vesicles in recipient cell glucose metabolism.

Introduction: Extracellular vesicles (EVs) are increasingly recognized as active coordinators of metabolic processes rather than mere messengers. By carrying unique subsets of enzymes, metabolites, lipids, and nucleic acids, EVs can directly deliver functional metabolic machinery or dynamically alter intracellular metabolic fluxes in recipient cells. However, their role in regulating specific biochemical pathways remains largely unknown. Methodology: In the current Results: Enrichment analysis of these mRNAs and proteins revealed that carbohydrate metabolic pathways, including glycolysis, the pentose phosphate pathway and the TCA cycle, were over-represented in EVs. Further, to investigate whether EVs carry miRNAs that regulate these pathways, we analyzed the miRNA targets. Enrichment analysis of EV miRNA targets mapped glycolytic regulatory genes, including Discussion: While the study has limitations-mainly due to the biological heterogeneity of EVs and the difficulty of standardizing cargo-the results potentially suggest that, by delivering enzymes, their mRNAs, regulatory miRNAs or combinations thereof, EVs could potentially mediate recipient cell glucose metabolism.