Furthermore, we also demonstrated that hyperactivity of ERK1/2 and JNK/c-Jun signaling induced by BAP1 downregulation was necessary for ICC cell proliferation, cell cycle progression, and invasion in vitro and in vivo using the inhibitors of the ERK1/2 pathway (U0126) and JNK/c-Jun pathway (SP600125). Here, MAPK3 is linked to intrahepatic cholangiocarcinoma.