Abstract: Objective Aldo-keto reductase family 1 member B10 (AKR1B10) plays an important role in the proliferation and metastasis of malignant tumors including hepatocellular carcinoma (HCC). However, the role of AKR1B10 in HCC glycolysis is not fully understood. Therefore, this study aims to explore the function of AKR1B10 in HCC glycolysis and investigate its potential mechanism. Methods The expression of AKR1B10 in HCC was analyzed by bioinformatics. The expression of AKR1B10 was detected by Real-time reverse transcription PCR (qRT-PCR) and Western blotting. Cell Counting Kit 8 (CCK-8), Transwell assay and flow cytometry were used to detect the cell proliferation, migration, invasion and apoptosis, respectively. The expression levels of Myelocytomatosis (MYC), hexokinase 2 (HK2) and phosphoglycerate kinase 1 (PGK1) were detected by qRT-PCR. Seahorse XP96 was used to analyze the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). The levels of pyruvate, lactic acid, citric acid and malic acid were detected by kits. Results The bioinformatic analysis showed that AKR1B10 was highly expressed in HCC tissues and cells, and GSEA analysis showed that glycolytic pathway was enriched. Overexpression of AKR1B10 could promote the proliferation, migration and invasion of HCC cells, and inhibit the cell apoptosis. In addition, the overexpression of AKR1B10 could promote the expression of MYC, HK2 and PGK1 in HCC cells, and improve the level of glycolysis. Glycolysis inhibitors (2-Deoxy-D-Glucose, 2-DG) could reverse the effect of AKR1B10 on the proliferation, migration, and invasion in HCC cells. Conclusion AKR1B10 can promote the HCC proliferation by activating glycolytic pathway, suggesting that AKR1B10 may be a new diagnostic marker and therapeutic target for HCC.

Key words: AKR1B10, glycolysis, hepatocellular carcinoma, proliferation, apoptosis