Ubiquitin-Specific Protease 12-Mediated Stabilization of KDM1A Facilitates Ovarian Cancer Progression Through Activation of the Akt/mTOR/p70S6K Signaling Pathway

Abstract

Ovarian cancer is still incurable, and new target genes are needed for further study. USP12 plays a crucial role in tumor progression, but its precise mechanism in ovarian cancer is not fully understood. RT-qPCR and western blot confirmed the expression level of USP12. The effect of USP12 on the proliferation, migration, and invasion of cells was examined through overexpression and silencing experiments, and key molecular signaling pathways were validated through western blotting. The relationship between USP12 and KDM1A expression was analyzed by Pearson correlation coefficient. Co-IP and western blot were used to conduct mechanistic studies. Mice xenografts were used to evaluate USP12’s function in vivo. Western blotting showed that USP12 is highly expressed and correlated with poor overall survival. USP12-overexpressing promoted cell processes in HO8910 cells, while USP12-silencing inhibited them in SKVO3 cells. KDM1A was significantly increased and had a positive relation with USP12 expression at the protein level. Co-IP experiments demonstrated that USP12 regulated KDM1A expression in a ubiquitin-dependent way. USP12 promoted ovarian cancer progress by stabilizing KDM1A, as shown by rescue experiments. in vivo studies showed that USP12-overexpressing promoted tumor growth and USP12-silencing inhibited it. Our results demonstrated that USP12 stabilized KDM1A to promote ovarian cancer progress via the Akt/mTOR/p70S6K signaling pathway, suggesting a new therapeutic target for ovarian cancer.