Mutation of in Cholangiocarcinoma Impairs Tumor Progression by Inhibiting Isocitrate Metabolism.

Isocitrate dehydrogenase 1 (IDH1) is key enzyme involved in cellular metabolism and DNA repair. Mutations in IDH1 occur in up to 25% of cholangiocarcinomas. The present study aimed to explore the features of cellosaurus REB cells with mutant and wide-type . To compare the features of knockout and mutation in cholangiocarcinoma, we firstly constructed the knockout and mutation cell lines. We then evaluated the viability of these cell lines using the cell count assay and MTT assay. Next, we determined cell migration and invasion using the Transwell assay. Additionally, to evaluate the effects of IDH1 on cellular metabolism, the levels of α-ketoglutarate (α-KG) and nicotinamide adenine dinucleotide phosphate (NADPH) were determined using enzyme-linked immunosorbent assay. We then applied ChIPbase dataset to explore the genes that were regulated by . High frequency of mutated was observed in the cholangiocarcinoma and R132C was presented in more than 80% of mutations. The results showed that knockout decreased cell proliferation, migration and invasion, whereas the overexpression of in knockout cell line recovered its proliferation, migration and invasion capacities. Additionally, mutation reduced the levels of NADPH and α-KG. Furthermore, investigation into the underlying mechanisms revealed that overexpression induced the expression of aldehyde dehydrogenase 1 thereby promoting cell proliferation, migration and invasion. plays an important role in cholangiocarcinoma and its mutation impairs tumor progression in part by inhibition of isocitrate metabolism.