Enhancer of zeste 2 polycomb repressive complex 2 subunit promotes sorafenib resistance of hepatocellular carcinoma though insulin-like growth factor 1 receptor

In this study, we demonstrated that EZH2 induced sorafenib resistance of HCC cells in vitro. Mechanistically, EZH2 was a potent regulator of insulin-like growth factor 1 receptor (IGF1R) and EZH2-modulated IGF1R expression by directly transcriptionally repressing a set of microRNAs (miRNAs) including miR-101, miR-122, miR-125b, and miR-139. These miRNAs were required for EZH2-mediated sorafenib resistance by promoting IGF1R expression. Surprisingly, IGF1R inhibitors significantly reversed EZH2-induced sorafenib resistance. Collectively, we proposed a novel model for an EZH2 – miRNAs – IGF1R regulatory axis, which might provide insights into how EZH2 contributes to sorafenib resistance in HCC.
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research