Circular RNA circ-ADD3 inhibits hepatocellular carcinoma metastasis through facilitating EZH2 degradation via CDK1-mediated ubiquitination.

Abstract

. Mechanistically, circ-ADD3 was capable of reinforcing the interaction between CDK1 and EZH2, resulting in increased EZH2 ubiquitination and subsequent degradation via phosphorylation at Thr-345 and Thr-487 sites. The decreased EZH2 markedly increased the expression of a cohort of anti-metastatic genes, including circ-ADD3, by reducing H3K27me3 levels on their promoter regions, which formed a regulatory circuit, thereby dampening HCC metastasis. Taken together, our findings unveil the essential role of circ-ADD3 in inhibiting HCC metastasis through regulation of EZH2 stability.