Glypican-3 knockdown inhibits the cell growth, stemness, and glycolysis development of hepatocellular carcinoma cells under hypoxic microenvironment through lactylation

ContextHepatocellular carcinoma (HCC) is a common malignant tumour in China. Glypican-3 (GPC3) is reported to be closely related to the occurrence and development of various tumours.ObjectiveThis study aimed to explore the role of GPC3 in HCC.Materials and methodsThe cell behaviours were investigated using Cell Counting Kit-8 (CCK-8), Traswell, and sphere formation assays. The protein and mRNA expression levels were detected using western blot and Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) assays.ResultsThe results showed that GPC3 knockdown decreased the cell viability and stemness, glucose uptake, lactate production, and extracellular acidification rate (ECAR), while increased the oxygen consumption rate (OCR) in hypoxia-treated HCC cells. Additionally, GPC3 knockdown decreased the global lactylation and c-myc lactylation, which further decreased the protein stability and expressions of c-myc.Discussion and conclusionGPC3-mediated lactylation modification may be a new direction in HCC treatment in the future.