DNA hypomethylation of the promoter and increased mRNA levels of secreted frizzled‐related protein 1 (SFRP1) were observed in CCA cells following the inhibition of polycomb repressor complex 2 (PRC2), which was achieved through a knockout of EZH2, SUZ12 and EED, respectively, or treatment with GSK126 and GSK343. The gene discussed is SFRP1; the disease is cholangiocarcinoma.