In addition, the promoter region demethylation of H3K27me3 modification in ICC also contributes to the upregulation of expression of VIRMA, and subsequently promotes ICC proliferation and metastasis via TMED2/Akt/GSK/β-catenin and PARD3B/ MEK/ERK/Slug pathways [90]. This evidence concerns the gene TMED2 and intrahepatic cholangiocarcinoma.