Hepatocellular carcinoma (HCC) is one of the malignancies with the worst prognosis worldwide, in the occurrence and development of which glycolysis plays a central role. This study uncovered a mechanism by which ZNF692 regulates ALDOA-dependent glycolysis in HCC cells. RT-qPCR and western blotting were used to detect the expression of ZNF692, KAT5, and ALDOA in HCC cell lines and a normal liver cell line. The influences of transfection-induced alterations in the expression of ZNF692, KAT5, and ALDOA on the functions of HepG2 cells were detected by performing MTT, flow cytometry, Transwell, cell scratch, and colony formation assays, and the levels of glucose and lactate were determined using assay kits. ChIP and luciferase reporter assays were conducted to validate the binding of ZNF692 to the KAT5 promoter, and co-IP assays to detect the interaction between KAT5 and ALDOA and the acetylation of ALDOA. ZNF692, KAT5, and ALDOA were highly expressed in human HCC samples and cell lines, and their expression levels were positively correlated in HCC. ZNF692, ALDOA, or KAT5 knockdown inhibited glycolysis, proliferation, invasion, and migration and promoted apoptosis in HepG2 cells. ZNF692 bound to the KAT5 promoter and promoted its activity. ALDOA acetylation levels were elevated in HCC cell lines. KAT5 bound to ALDOA and catalyzed ALDOA acetylation. ALDOA or KAT5 overexpression in the same time of ZNF692 knockdown, compared to ZNF692 knockdown only, stimulated glycolysis, proliferation, invasion, and migration and reduced apoptosis in HepG2 cells. ZNF692 promotes the acetylation modification and protein expression of ALDOA by catalyzing KAT5 transcription, thereby accelerating glycolysis to drive HCC cell development.

肝细胞癌（HCC）是全球预后最差的恶性肿瘤之一，糖酵解在其发生、发展中发挥着核心作用。这项研究揭示了 ZNF692 调节 HCC 细胞中 ALDOA 依赖性糖酵解的机制。采用RT-qPCR和蛋白质印迹法检测HCC细胞系和正常肝细胞系中ZNF692、KAT5和ALDOA的表达。通过MTT、流式细胞术、Transwell、细胞划痕、集落形成实验检测转染诱导的ZNF692、KAT5、ALDOA表达变化对HepG2细胞功能的影响，并检测葡萄糖、乳酸水平。使用测定试剂盒测定。进行 ChIP 和荧光素酶报告基因测定来验证 ZNF692 与 KAT5 启动子的结合，并进行 co-IP 测定来检测 KAT5 和 ALDOA 之间的相互作用以及 ALDOA 的乙酰化。ZNF692、KAT5和ALDOA在人HCC样本和细胞系中高表达，并且它们的表达水平在HCC中呈正相关。ZNF692、ALDOA 或 KAT5 敲低可抑制 HepG2 细胞的糖酵解、增殖、侵袭和迁移并促进细胞凋亡。ZNF692 与 KAT5 启动子结合并促进其活性。HCC 细胞系中 ALDOA 乙酰化水平升高。KAT5 与 ALDOA 结合并催化 ALDOA 乙酰化。与仅敲低 ZNF692 相比，在敲低 ZNF692 的同时，ALDOA 或 KAT5 过表达会刺激 HepG2 细胞的糖酵解、增殖、侵袭和迁移，并减少细胞凋亡。ZNF692通过催化KAT5转录促进ALDOA的乙酰化修饰和蛋白表达，从而加速糖酵解以驱动HCC细胞的发育。