PELNs suppress colorectal cancer by delivering miR-166 to target the SKI-c-Myc axis, thereby destabilizing c-Myc and triggering G1/S cell cycle arrest and apoptosis.
Colorectal cancer (CRC) remains a major therapeutic challenge, and effective strategies for suppressing its core oncogenic programs are still limited. Here, we investigated whether Platycodon grandiflorum-derived exosome-like nanovesicles (PELNs) exert antitumor activity in CRC through a defined vesicular microRNA–target axis. PELNs displayed characteristic nanovesicular features, were efficiently internalized by CRC cells, and suppressed tumor cell growth while inducing cell-cycle arrest and apoptosis. Small RNA profiling identified miR-166h as a highly enriched cargo in PELNs. Mechanistically, miR-166h directly targeted the 3'-untranslated region of SKI, leading to reduced SKI expression and attenuation of downstream ß-catenin/c-Myc signaling. This pathway collapse was associated with decreased proliferative signaling, reinforcement of cell-cycle checkpoint control, and activation of apoptotic programs. Restoration of SKI partially rescued the downstream signaling changes and antitumor phenotype, supporting SKI as a functionally relevant upstream node in this system. In vivo, PELN treatment inhibited tumor growth in both human HCT116 xenograft and murine CT26 syngeneic models, recapitulated suppression of the SKI–ß-catenin–c-Myc axis in tumor tissues, and showed no evidence of overt systemic toxicity. Collectively, these findings identify a mechanistically defined PELN–miR-166h–SKI axis and suggest that plant-derived nanovesicles may serve as biologically precise RNA-delivery platforms for targeting oncogenic transcriptional circuitry in colorectal cancer.
Colorectal cancer (CRC) remains a major therapeutic challenge, and effective strategies for suppressing its core oncogenic programs are still limited. Here, we investigated whether Platycodon grandiflorum-derived exosome-like nanovesicles (PELNs) exert antitumor activity in CRC through a defined vesicular microRNA–target axis. PELNs displayed characteristic nanovesicular features, were efficiently internalized by CRC cells, and suppressed tumor cell growth while inducing cell-cycle arrest and apoptosis. Small RNA profiling identified miR-166h as a highly enriched cargo in PELNs. Mechanistically, miR-166h directly targeted the 3'-untranslated region of SKI, leading to reduced SKI expression and attenuation of downstream ß-catenin/c-Myc signaling. This pathway collapse was associated with decreased proliferative signaling, reinforcement of cell-cycle checkpoint control, and activation of apoptotic programs. Restoration of SKI partially rescued the downstream signaling changes and antitumor phenotype, supporting SKI as a functionally relevant upstream node in this system. In vivo, PELN treatment inhibited tumor growth in both human HCT116 xenograft and murine CT26 syngeneic models, recapitulated suppression of the SKI–ß-catenin–c-Myc axis in tumor tissues, and showed no evidence of overt systemic toxicity. Collectively, these findings identify a mechanistically defined PELN–miR-166h–SKI axis and suggest that plant-derived nanovesicles may serve as biologically precise RNA-delivery platforms for targeting oncogenic transcriptional circuitry in colorectal cancer.