Moreover, IHC statistical analyses revealed positive correlations of RNF219 level with the expression of nuclear β‐catenin (p < 0.001, r = 0.502), nuclear YAP1 (p < 0.001, r = 0.270), and LGALS3 (p < 0.05, r = 0.644) but negative correlation with α‐catenin (p < 0.001, r = 0.509) (n = 475 and Figure 6B), which provided clinical evidence that RNF219‐mediated α‐catenin reduction activated both Wnt/β‐catenin and YAP1 pathways, consequently resulting in LGALS3 upregulation in HCC. Here, OBI1 is linked to hepatocellular carcinoma.