Potential Mechanism of Ginsenoside Re in Tumor Progression of Colorectal Cancer Through Affecting MmiR-4516

Abstract

This study aims to investigate whether G-Re exerts anti-tumor effects in CRC by modulating miR-4516. The anti-proliferative effect of G-Re was evaluated by CCK-8 (IC₅₀ calculation). MiR-4516 expression was detected via qRT-PCR. Functional assays (proliferation, migration, invasion) were performed after transfection with miR-4516 inhibitor/mimic and G-Re treatment. The miR-4516/ETV4 binding relationship was confirmed by dual-luciferase and RIP assays, with ETV4 expression examined. Rescue experiments were conducted by co-transfecting CRC cells with miR-4516 mimic and an ETV4 overexpression vector. G-Re inhibited the viability of HCT116 and SW480 cells, with IC₅₀ values of 25.28 µM and 26.65 µM, respectively. miR-4516 expression was lower in CRC cells than in NCM460 cells. Overexpression of miR-4516 suppressed CRC cell proliferation, migration, and invasion. Conversely, inhibition of miR-4516 partially reversed the anti-tumor effects of G-Re. Dual-luciferase and RIP assays verified that miR-4516 binds directly to the ETV4 3'UTR at the predicted site. ETV4 was highly expressed in the tested CRC cell lines. ETV4 overexpression significantly reversed the suppressive effects of miR-4516 on CRC cell proliferation, migration, and invasion. G-Re suppresses the progression of CRC, potentially through its association with the tumor-suppressive miR-4516. miR-4516 was confirmed to directly bind and inhibit ETV4. These findings point to a potential mechanism underlying the anti-CRC activity of G-Re, with the miR-4516/ETV4 axis representing a candidate therapeutic target.