Working model. As shown in the upper panel, in the absence of ligand, PPAR recruits NM23-H2 as a corepressor to inhibit proliferation and carcinogenesis. As shown in the lower panel, corepressors are released in the presence of ligand. In the absence of NM23-H2, PPAR transcriptional activity is enhanced. Increased PPAR transcriptional activity activates the PI3K/AKT signalling pathway to promote cholangiocarcinogenesis. PPAR, peroxisome proliferator-activated receptor; NM23-H2, nucleoside diphosphate kinase alpha; PI3K, phosphoinositide 3-kinase; Akt, protein kinase B.