Bridging Kingdoms: A CroSeed-Based pipeline to decipher grapes miRNA bio-activity in Human cells

Plant-derived microRNAs (miRNAs) are proposed to exert cross-kingdom gene regulation in humans by surviving digestion, entering circulation, and modulating host gene expression via the human RNA-induced Silencing Complex (RISC). This mechanism, which relies on the structural compatibility of plant miRNAs with RISC binding constraints (specifically the seed region g2–g8), suggests a potential dietary influence on human physiology. Methods: We developed CroSeed, a bioinformatics pipeline designed for comparative analysis between human and plant miRNAs. Using sequencing data from Aglianico and Cabernet Sauvignon grapevine cultivars, CroSeed employs a relational database integrated with human data repositories (KEGG, OMIM, OncoDB). The core algorithm assigns region-specific reliability scores (seed, central loop, supplementary region) to assess structural compatibility for RISC binding. The pipeline identifies grape miRNAs that functionally mimic endogenous human miRNAs and reconstructs associated human metabolic networks and disease implications. Results & Conclusion: Analysis identified 28 and 14 miRNAs in Cabernet Sauvignon and Aglianico, respectively, potentially targeting genes in oncogenic pathways. In vitro experiments confirmed that two selected miRNAs significantly reduced cell viability and induced apoptosis in mesothelioma, breast, and prostate cancer cells. The findings suggest broad implications, supporting the potential for grape-derived miRNAs to offer health benefits and act as a foundation for developing functional foods and novel miRNA-based therapeutics