Hypoxia-induced PPFIA4 accelerates the progression of ovarian cancer through glucose metabolic reprogramming.

Dysregulated glycolysis promotes growth and metastasis, which is one of the metabolic characteristics of ovarian cancer. Based on bioinformatics analysis, liprin-alpha-4 (PPFIA4) is a gene associated with hypoxia, and we aimed to investigate the potential mechanism of PPFIA4 during the reprogramming of glucose metabolism in ovarian cancer cells. Currently, the cell viability of ovarian cancer cells under the hypoxia treatment was evaluated by CCK-8 assay, and cell migration and invasion were measured by transwell assay and western blot. The effects of hypoxia treatment on glucose uptake, lactate production, extracellular acidification rate (ECAR), adenosine triphosphate (ATP), reactive oxygen species (ROS), Nicotinamide adenine dinucleotide phosphate (NADPH) and its oxidized form NADP + , and oxygen consumption rate (OCR) in ovarian cancer cells were examined. Then PPFIA4 was identified through bioinformatic analysis, and the regulatory effects of PPFIA4 on glucose metabolic reprogramming. Our data suggested that hypoxia enhanced the migration and invasion ability of ovarian cancer cells in vitro, and promoted the glucose metabolic reprogramming of ovarian cancer cells. Ovarian cancer cell viability, migration, and invasion were inhibited after PPFIA4 knockdown. Inhibition of PPFIA4 inhibited hypoxic-induced glucose metabolic reprogramming in ovarian cancer cells. In addition, PPFIA4 was found to bind to hypoxia-inducible factor 1alpha (HIF1A), and HIF1A prominently induced PPFIA4 expression. Collectively, HIF1A mediated upregulation of PPFIA4 and promoted reprogramming of glucose metabolism in ovarian cancer cells. Therefore, PPFIA4 may be a therapeutic target for ovarian cancer intervention.