Discovering Anticancer Effects of Phytochemicals on MicroRNA in the Context of Data Mining

<b>Background</b>: miRNA is linked to a variety of human diseases, including cancer. The expression levels and profiles can be related to disease prevention and the promotion of good health. Understanding the beneficial changes in miRNA expression mediated by micro- and macronutrients is vital for maintaining optimal health. However, it remains unknown which phytochemicals affect miRNA expression, thereby hindering the identification of novel dietary functions. <b>Methods</b>: We searched for and investigated novel phytochemicals that would regulate miRNAs in colon cancer using artificial intelligence. We comprehensively analyzed miRNA expression in colon cancer cell lines treated with new phytochemical candidates using next-generation sequencing. <b>Results</b>: We identified three phytochemicals (fisetin, glabridin, and silibinin) that suppressed cell proliferation and were associated with changes in cancer-related miRNA expression in colon cancer cells. The miRNA expression profiles observed in response to each phytochemical shared some common features while also displaying compound-specific miRNA signatures. Exploratory pathway analyses of fisetin, glabridin, or silibinin have shown that each affects pathways involved in tumor development, including the p53 signaling pathway, apoptosis, cellular senescence, and colorectal cancer. <b>Conclusions</b>: The use of artificial intelligence to explore candidate compounds is beneficial, leading to the discovery of new phytochemicals modulating tumor-related miRNAs. Investigating the mechanisms of action of miRNAs will be essential for understanding new functions of dietary nutrients, thereby providing further insights into the development of diet-based health promotion and disease prevention strategies.