Fig. 4.
JMJD4-demethylated RIG-I inhibits DEN-induced hepatocarcinogenesis. a JMJD4-RIG-I association induced by IL-6 was examined by immunoprecipitation in male mouse liver tissues. b Methylated RIG-I at K18 and K146 upon IL-6 stimulation was examined in male Jmjd4f/f and Jmjd4hep−/− liver tissues and isolated primary hepatocytes as indicated. c IL-6-induced RIG-I-STAT3 association was evaluated by immunoprecipitation in liver tissues from male Jmjd4f/f and Jmjd4hep−/− mice. d IL-6-induced STAT3 phosphorylation was evaluated in liver tissues from male Jmjd4f/f and Jmjd4hep−/− mice upon IL-6 stimulation. e Tumor incidence (chi-square test), number and maximum diameter (unpaired t-test) of DEN-induced HCC in Jmjd4f/f and Jmjd4hep−/− mice were analyzed (n = 12). f JMJD4 expression in isolated normal hepatocytes, nonaggregated hepatocytes and HcPCs from male mice five months post-DEN injection, and established HCC cells eight months post-DEN injection was examined by Western blot. g Tumor incidence (chi-square test), number and maximum diameter (unpaired t-test) of DEN-induced HCC in male Jmjd4f/fRig-If/f, Rig-Ihep−/− and Jmjd4hep−/−Rig-Ihep−/− mice, or in male Jmjd4f/f, Jmjd4f/f RIG-I K18A+K146A and Jmjd4hep−/− RIG-I K18A+K146A mice as indicated were analyzed (n = 12). h IL-6-induced STAT3 phosphorylation was evaluated in liver tissues from male Jmjd4f/fRig-If/f, Rig-Ihep−/− and Jmjd4hep−/−Rig-Ihep−/− mice upon IL-6 stimulation. Data are shown as mean ± s.d. or photographs from one representative of three independent experiments. *P < 0.05, **P < 0.01, ▲P > 0.05