Dioscin suppresses proliferation and metastasis of osteosarcoma by inhibiting HuR/Pim1 axis via the induction of miR-16-5p level

Abstract

DS suppressed the growth of solid tumor and inhibited HuR/Pim1 in mice model in a miR-16-5p induction-dependent manner. • DS suppresses proliferation and metastasis of osteosarcoma. • The anti-OS function of DS is associated with the function of miRs. • MiR-16-5p plays an indispensable role in the anti-OS function of DS. Dioscin (DS) is a natural compound with inhibitory effects on multiple cancer types and we explored the mechanism driving the antagonizing effect of DS on osteosarcoma (OS). OS cell lines were treated with DS and microRNAs (miRs) responding to DS treatment were determined. Effects of DS on viability, apoptosis, metastasis, and miR-16-5p/HuR/Pim1 pathway activity were assessed. MiR-16-5p was inhibited before DS treatment to confirm its central role in anti-OS effects of DS. The conclusion derived from in vitro assays was verified with a mouse model. DS suppressed viability, invasion and migration, while induced apoptosis in OS cells. Moreover, the compound also induced the expression of miR-16-5p, contributing to the inhibition of HuR/Pim1 pathway. The inhibited expression of miR-16-5p counteracted the anti-OS function of DS, which was also validated in mice. Anti-OS effects of DS depended on the induction of miR-16-5p, making the compound a promising adjuvant agent for treating OS.