The roles of non-coding RNAs in cardiometabolic health-promoting properties of (poly)phenols

(Poly)phenols are secondary plant metabolites with various biological roles. Approximately 8,000 (poly)phenols have been identified in plants, several hundred of which are relevant to human nutrition. Studies have shown that dietary (poly)phenols can have beneficial health effects, such as decreasing insulin resistance, improving blood lipids and vascular function, and reducing the risk for cardiovascular diseases. However, studies have also highlighted significant inter-individual variabilities in the health-promoting effects of (poly)phenols, phenomena that require complex, in-depth analyses to fully understand. At the molecular level, the health-promoting effects of (poly)phenols are linked to the genomic modifications, including changes in both protein coding and non-coding genes. Among the non-coding RNAs, several types of RNA molecules exist, such as miRNAs, lncRNAs, snoRNAs, and circRNAs. Of these, miRNAs, and to some extent lncRNAs, are the most extensively studied. The involvement of non-coding genes in the health-promoting effects of (poly)phenols has become increasingly evident through the use of untargeted transcriptomic analytical approaches. Elucidation of their cellular effects and molecular mechanisms of action is an important task. A systematic literature search identified 27 miRNAs significantly associated with the beneficial cardiometabolic health effects of (poly)phenols in humans. Additionally, a human intervention study demonstrated that 6 miRNAs and 244 lncRNAs were significantly modulated by the consumption of an extract of (poly)phenol-rich beverage. We utilized databases and bioinformatic tools, such as Mienturnet and LncRRIsearch, to identify miRNA- and lncRNA-targets, respectively. Following this, we conducted pathway enrichment analyses to elucidate the biological roles of the modulated non-coding RNAs. These analyses identified several cellular pathways significantly affected by dietary (poly)phenols at the miRNA level, including PI3K-Akt signalling pathway, Ras signalling pathway, MAPK signaling pathway, chemokine signaling pathway, and focal adhesion. At the lncRNA level, the affected pathways include tight junction, Ras signalling pathway, phytochemical activity on NRF2 transcriptional activation, and apoptosis. Subsequent multi-level bioinformatic analyses, which integrated genomic modulations at the mRNA, miRNA, and lncRNA level, identified several common cellular pathways. Notably, focal adhesion consistently emerged as one of the key cellular pathways significantly modulated by dietary (poly)phenols. These transcriptomic and integrative bioinformatic analyses, aimed at identifying the subtle molecular mechanisms of action of (poly)phenols, revealed key cellular processes and pathways affected by dietary (poly)phenols at the level of non-coding RNAs. The results of these analyses could help elucidate genetically induced inter-individual variabilities in the cardiometabolic health-protective properties of (poly)phenols, potentially paving the way for development of personalized nutrition recommendations.