Equilibrative nucleoside transporter 3 promotes the progression of hepatocellular carcinoma by regulating the AKT/mTOR signaling pathway

Equilibrative nucleoside transporter 3 (ENT3) belongs to the solute carrier family 29. Nucleoside transporters encoded by ENT3 play an important role in the uptake of nucleosides, nucleobases, and their nucleoside analogs, as well as participate in and regulate several physiological activities. However, no study has so far reported the role of ENT3 in hepatocellular carcinoma (HCC). We employed bioinformatics to analyze the expression, prognosis, and mechanism of ENT3 in HCC, as well as verified the same through biological experiments including cell proliferation, cell migration and invasion, and cell cycle and apoptosis, along with the detection of the AKT/mTOR protein expression in the pathway by Western blotting. ENT3 was widely and highly expressed in pan-cancer and upregulated in HCC. The upregulated ENT3 was related to the poor prognosis and clinical features in HCC patients. ENT3 knockdown inhibited cell proliferation, migration, and invasion and promoted cell apoptosis. ENT3 knockdown reduced the p-AKT and p-mTOR protein phosphorylation level, inhibited p-p70S6K1 and increased the p-4EBP1-the downstream effector of the AKT/mTOR pathway-protein phosphorylation level. Our study findings demonstrated that the expression of ENT3 was upregulated in HCC, which represents a poor prognosis. Thus, ENT3 promotes the progression of HCC through the AKT/mTOR signaling pathway.