CircEZH2 promotes gallbladder cancer progression and lipid metabolism reprogramming through the miR-556-5p/SCD1 axis.

ABSTRACT

Gallbladder cancer (GBC) is characterized by a high degree of malignancy and a poor prognosis. This study revealed that circEZH2 was frequently upregulated in GBC tissues and correlated with advanced tumor-node-metastasis (TNM) stage in GBC patients. In vitro and in vivo experiments confirmed that circEZH2 promoted the proliferation and inhibited the ferroptosis of GBC. Besides, this study discovered that circEZH2 regulated lipid metabolism reprogramming in GBC cells. Mechanistically, circEZH2 promotes SCD1 expression by sponging miR-556-5p in GBC cells. In addition, IGF2BP2 enhances the stability of circEZH2 in an m6A-dependent manner, while circEZH2 suppresses the ubiquitination and degradation of IGF2BP2 by binding to IGF2BP2. Taken together, our findings indicated that circEZH2, upregulated via a positive feedback loop between circEZH2 and IGF2BP2, promotes GBC progression and lipid metabolism reprogramming through the miR-556-5p/SCD1 axis in GBC. circEZH2 may serve as a potential therapeutic target for GBC.