In this study, we investigated the role of TUG1 in the pathogenesis of intrahepatic cholangiocarcinoma (ICC).TUG1 is upregulated in ICC samples, which correlates with poor prognosis and adverse clinical pathological characteristics. Knockdown of TUG1 inhibited the proliferation, motility, and invasiveness of cultured ICC cells, and decreased tumor burden in a xenograft mouse model. When we explored the mechanisms underlying these effects, we found that TUG1 acts as an endogenous competing RNA (ceRNA) that â??spongesâ?? miR-145, thereby preventing the degradation of Sirt3 mRNA and increasing expression of Sirt3 and GDH proteins. Accordingly, glutamine consumption, a-KG production, and ATP levels were dramatically decreased by TUG1 knockdown in ICC cells, and this effect was reversed by miR-145 inhibition. These findings indicate that the TUG1/miR-145/Sirt3/GDH regulatory network may provide a novel therapeutic strategy for treatment of ICC.