ACLY-β-catenin axis modulates hepatoblastoma cell proliferation

HB (hepatoblastoma) is most common in children with liver cancer and few options for treating HB. Thus, it is of great significance to investigate the regulatory mechanism of HB and/or identify new therapeutic targets for clinical treatment of HB. Here, we showed that ACLY (ATP citrate lyase), an important lipometabolic enzyme for de novo biosynthesis of fatty acids and steroids, has a higher expression in HB tissues than noncancerous tissues, and is required for HB cell proliferation. Moreover, knocking down ACLY in HB cells caused severe S-phase arrest and apoptosis. Mechanistically, ACLY knockdown significantly silenced the Wnt signaling pathway and reduced beta-catenin expression in HB cells. Conversely, the apoptotic alleviation of HB cells by overexpressing ACLY was blocked by silencing beta-catenin, suggesting the modulation of HB cells by ACLY-beta-catenin axis. Our results uncovered the role of ACLY in HB cells and presented a theoretical approach for HB targeted therapy in the future. (c) 2023 Elsevier Inc. All rights reserved.

Automated summary

HB is the most common type of liver cancer in children with limited treatment options. Understanding the regulatory mechanism of HB and identifying new therapeutic targets are crucial. This study found that ACLY, a key enzyme involved in lipid metabolism, is highly expressed in HB tissues and essential for HB cell proliferation. Knocking down ACLY resulted in cell cycle arrest and apoptosis in HB cells. Mechanistically, ACLY knockdown suppressed the Wnt signaling pathway and decreased the expression of beta-catenin in HB cells. Overexpression of ACLY alleviated apoptosis in HB cells, which was blocked by silencing beta-catenin, suggesting a role of ACLY-beta-catenin axis in modulating HB cells. These findings provide insights into the role of ACLY in HB cells and offer a theoretical approach for targeted therapy in the future.