MicroRNA signatures in ginseng derived exosome-like vesicles reveal functional RNAs for anti-tumor activity

To elucidate the complex and delicate biological mechanisms and functions of ginseng-derived exosome-like vesicles (gEVs), gEVs from different ginseng parts with different cultivation periods (3-year-old, 4-year-old, and 6-year-old ginseng) were comparatively examined in terms of their physicochemical properties, microRNA (miRNA) profiles, and anticancer effects. We demonstrated that the higher amounts of gEVs exist in lateral roots than in main roots of ginsengs. The gEVs from 4-year-old ginseng main/lateral root (4mlEV) and gEVs from 6-year-old ginseng main/lateral root (6mlEV) exhibited promising antiproliferation and antimigration effects in breast and colon cancer cells without notable toxicity. Based on the miRNA sequencing analysis of gEVs, two selected miRNAs, namely pgi-miR6136a.2 and Seq46-1, elicited notable antiproliferation and antimigration in breast and colon cancer cells. In particular, combination of two potent miRNAs (Combi) showed high efficacy in colon cancer cells. Administration of Combi in lipid nanoparticles (Combi@LNP) greatly suppressed tumor growth for CT26 xenograft model in vivo by attenuating expression of Bcl-2 and cyclin D1 for apoptosis and cell cycle arrest. In this study, we found that the anticancer effect of gEVs might be attributed to the interior miRNAs and confirmed that this newly identified miRNAs alone induce remarkable anticancer effects in colon cancer cells. Thus, these results clearly demonstrated that the gEV-derived miRNAs could serve as potent nucleic acid-based anticancer drugs for colon cancers.