HBXIP Regulates Gastric Cancer Glucose Metabolism and Malignancy Through PI3K/AKT and p53 Signaling.

INTRODUCTION: Hepatitis B X-interacting protein (HBXIP) overexpression is related to the progression of multiple cancers. However, its role in gastric cancer (GC) remains unclear. MATERIALS AND METHODS: HBXIP expression was determined in human GC specimens and cell lines by quantitative polymerase chain reaction (qRT-PCR) and Western blot. The effects of HBXIP depletion or ectopic expression on GC proliferation were evaluated in vitro using the cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation, and cell cycle assays. The in vivo effects were investigated using a mouse xenograft model. Apoptosis was evaluated by flow cytometry (in vitro) and immunohistochemistry (IHC; in vivo). Cell migration and invasion were evaluated in vitro using wound healing, transwell migration, and matrigel invasion assays; and in vivo by quantifying distant metastases from injection of GC cells in the lateral tail vein. RESULTS: Herein, we reported that HBXIP expression was higher in GC than in normal tissues, and this high expression indicated a poorer prognosis. Gain- and loss-of-function assays showed that HBXIP promoted GC proliferation, migration, and invasion, and inhibited apoptosis. High-performance liquid chromatography (HPLC) quantification of glycolytic metabolites revealed that HBXIP promoted glucose metabolic reprogramming. Investigation of the PI3K/AKT and p53 pathways highlighted their role in this HBXIP-mediated metabolic reprogramming. CONCLUSION: Our results indicate that the up-regulation of HBXIP leads to GC progression by positively regulating glucose metabolism. Therefore, HBXIP is a potential target for the treatment of GC.