Silencing Of ECHS1Attenuates The Proliferation And Induces Autophagy Of Hepatocellular Carcinoma Via Impairing Cell Metabolism And Activating AMPK

Background and aims: Hepatocellular carcinoma (HCC) is one of the mostcommon cancers with low survival rate in the world. The lack of good diagnosticmarkers and treatment strategies has rendered the disease a major challenge. Inrecently, molecular targeted therapies in Hepatocellular Carcinoma become a noveltrial. The aim of this study was to investigated ECHS1functions during thedevelopment of HCC, and found out the changes of energy metabolism and effects onHepatocellular carcinoma cells.Methods：We successfully established human HepG2and Huh-7cell lines inwhich ECHS1was stably knocked down; Then detected the proliferation ofsiECHS1-HepG2and siECHS1-Huh-7comparing with their control cells using CCK8and EdU cell proliferation assay. We measured the level of ATP and NADPH incellular by the ATP colorimetric assay kit and NADP+/NADPH colorimetric kit.Weused the western blot to demonstrate the changes of kinases in energy metabolism andthe expression of LC3which represent of autophagy, and performed confocalmicroscopy analysis on LC3-Ⅱ fluorescence for comparing the autophagy insiECHS1cells with control cells.Results： We have demonstrated that silencing of ECHS1attenuated cellproliferation and activated AMPK which led to cell autophagy in HCC. Furthermore,silencing of ECHS1not only decreased the fatty acid oxidation but also impaired fattyacid synthesis. In addition, our result show that knockdown of ECHS1decreased levelof the cellular ATP and NADPH.Conclusion: Our results demonstrated that silence ECHS1inhibited cellproliferation and induced cell autophagy. These findings suggest that ECHS1may beapplied as a potential therapeutic target during the treatment of HCC.