Plant-Derived miRNAs as Potential Cross-Kingdom Cancer Regulators

MicroRNAs (miRNAs) are key posttranscriptional regulators of gene expression that influence cancer initiation, progression, and therapeutic response. While most studies have focused on endogenous miRNAs, emerging evidence has highlighted the role of plant-derived miRNAs as exogenous dietary regulators capable of cross-kingdom gene modulation. This review summarises current knowledge regarding plant-derived miRNAs and their ability to regulate human cancer-related genes. Experimental findings indicate that plant miRNAs can withstand gastrointestinal digestion, enter the circulation, and regulate the expression of oncogenes, tumour suppressors, long noncoding RNAs, and immune checkpoint molecules via canonical RNA-induced silencing mechanisms. Specific examples include miR-156a, miR-159a-3p, miR-166a, miR-167e-5p, miR-171, miR-395e, miR-2911, miR-4995 and miR-5754, which exhibit anticancer activities across various cancer types and modulate key signalling pathways in mammalian cells, highlighting their potential as cross-kingdom regulators with therapeutic relevance. In addition to these characterised miRNAs, certain plant groups, which are rich in bioactive compounds, remain unexplored as sources of functional miRNAs, representing a promising avenue for future research. Collectively, these studies underscore the ability of plant-derived miRNAs to modulate mammalian gene expression and suggest their potential as diet-based or synthetic therapeutic agents. Further investigations into their bioavailability, target specificity, and functional relevance could inform innovative strategies for cancer prevention, integrating nutritional, molecular biological, and therapeutic approaches.