Modulating Effects of Cancer-Derived Exosomal miRNAs and Exosomal Processing by Natural Products

SIMPLE SUMMARY: Cancer cells generate exosomes (extracellular vesicles) to regulate many cell functions for tumor progression. Many exosome-modulating clinical drugs have been developed for effective cancer therapy, but the functions and exosome processing (secretion and assembly) modulation by natural products are not well understood. In this review, we fill the gaps between natural products-modulated miRNAs and exosome-processing by the target gene prediction of the bioinformatics database. The cancer-derived exosomal miRNAs and their exosome processing and modulated cell functions by natural products are well organized. Consequently, this review provides a comprehensive and potential modulating mechanism and targets for exosome processing and cancer cell functions for natural products. ABSTRACT: Cancer-derived exosomes exhibit sophisticated functions, such as proliferation, apoptosis, migration, resistance, and tumor microenvironment changes. Several clinical drugs modulate these exosome functions, but the impacts of natural products are not well understood. Exosome functions are regulated by exosome processing, such as secretion and assembly. The modulation of these exosome-processing genes can exert the anticancer and precancer effects of cancer-derived exosomes. This review focuses on the cancer-derived exosomal miRNAs that regulate exosome processing, acting on the natural-product-modulating cell functions of cancer cells. However, the role of exosomal processing has been overlooked in several studies of exosomal miRNAs and natural products. In this study, utilizing the bioinformatics database (miRDB), the exosome-processing genes of natural-product-modulated exosomal miRNAs were predicted. Consequently, several natural drugs that modulate exosome processing and exosomal miRNAs and regulate cancer cell functions are described here. This review sheds light on and improves our understanding of the modulating effects of exosomal miRNAs and their potential exosomal processing targets on anticancer treatments based on the use of natural products.