biostudies-literatureWang YDNCI NIH HHSPHS HHS322-31https://www.ebi.ac.uk/biostudies/studies/S-EPMC4318883biostudies-literatureUnknown29(2)The farnesoid X receptor (FXR) is a key metabolic and homeostatic regulator in the liver. In the present work, we identify a novel role of FXR in antagonizing c-Jun N-terminal kinase (JNK) signaling pathway in liver carcinogenesis by activating superoxide dismutase 3 (SOD3) transcription. Compared with wild-type mouse liver, FXR(-/-) mouse liver showed elevated JNK phosphorylation. JNK1 deletion suppressed the increase of diethylnitrosamine-induced tumor number in FXR(-/-) mice. These results suggest that JNK1 plays a key role in chemical-induced liver carcinogenesis in FXR(-/-) mice. We found that ligand-activated FXR was able to alleviate H₂O₂or tetradecanoylphorbol acetate-induced JNK phosphorylation in human hepatoblastoma (HepG2) cells or mouse primary hepatocytes. FXR ligand decreaseMolecular endocrinology (Baltimore, Md.)Farnesoid X receptor antagonizes JNK signaling pathway in liver carcinogenesis by activating SOD3.PMC4318883R01-139158R01 CA139158P30 CA033572Li YYuan FChen WDLi CLong XQi HHuang WWang YDGuo CWang XKong JShen HfalseFarnesoid X receptor antagonizes JNK signaling pathway in liver carcinogenesis by activating SOD3.The farnesoid X receptor (FXR) is a key metabolic and homeostatic regulator in the liver. In the present work, we identify a novel role of FXR in antagonizing c-Jun N-terminal kinase (JNK) signaling pathway in liver carcinogenesis by activating superoxide dismutase 3 (SOD3) transcription. Compared with wild-type mouse liver, FXR(-/-) mouse liver showed elevated JNK phosphorylation. JNK1 deletion suppressed the increase of diethylnitrosamine-induced tumor number in FXR(-/-) mice. These results suggest that JNK1 plays a key role in chemical-induced liver carcinogenesis in FXR(-/-) mice. We found that ligand-activated FXR was able to alleviate H₂O₂or tetradecanoylphorbol acetate-induced JNK phosphorylation in human hepatoblastoma (HepG2) cells or mouse primary hepatocytes. FXR ligand decrease2015-01-01T00:00:00Z2015 Feb2025-04-20T02:51:18.762Z2019-03-27T01:44:43ZS-EPMC43188832549603310.1210/me.2014-1225