CYP2E1 plays a suppressive role in hepatocellular carcinoma by regulating Wnt/Dvl2/β-catenin signaling

• DOI: 10.1186/s12967-022-03396-6
• Publication Date: 2022-05-04T11:02:58Z
• Authors: Lili Zhu; Xiaobei Yang; Jingyu Feng; Jian Mao; Qidong Zhang; Mengru He; Yang Mi; Yingwu Mei; Ge Jin; Haifeng Zhang
• Keywords: Ectopic expression

Knowledge of the role CYP2E1 in hepatocarcinogenesis is largely based on epidemiological and animal studies, with a primary focus metabolic activation procarcinogens. Few studies have directly assessed effects HCC malignant phenotypes.The expression tissues was determined by qRT-PCR, western blotting immunohistochemistry. Overexpression cell achieved lentivirus transfection. The function were detected CCK-8, wound healing, transwell assays, xenograft models pulmonary metastasis model. TOP/FOPFlash reporter assay, blotting, functional rescue experiments, Co-immunoprecipitation reactive oxygen species detection conducted to reveal underlying mechanism tumor suppressive CYP2E1.CYP2E1 down-regulated tissues, this downregulation associated large diameter, vascular invasion, poor differentiation, shortened patient survival time. Ectopic inhibits proliferation, invasion migration epithelial-to-mesenchymal transition cells vitro, formation lung nude mice. Mechanistic investigations show that overexpression significantly inhibited Wnt/β-catenin signaling activity decreased Dvl2 cells. An increase restored phenotype Notably, promoted ubiquitin-mediated degradation strengthening interaction between E3 ubiquitin ligase KLHL12 CYP2E1-stable CYP2E1-induced ROS accumulation critical upstream event Wnt/β-Catenin pathway CYP2E1-overexpressing cells.These results provide novel insight into suppressor can be attributed its ability manipulate Wnt/Dvl2/β-catenin via inducing accumulation, which provides potential target for prevention treatment HCC.