Overexpression of PFKFB3 Promotes Cell Glycolysis and Proliferation in Renal Cell Carcinoma

Abstract Background: Cancer cells prefer aerobic glycolysis to increase their biomass and sustain uncontrolled proliferation. As a key glycolytic activator, phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) has been implicated in the progression of multiple types of tumors. However, the specific function and clinical significance of PFKFB3 in renal cell carcinoma (RCC) remain unclear. In the present study, we explored the role of PFKFB3 in RCC.Methods: We analyzed the expression of PFKFB3 in clear cell renal cell carcinoma (ccRCC) tissues and its relationship with clinical characteristics of ccRCC. Real-time PCR and Western blot analysis were used to detect PFKFB3 expression levels in different RCC cell lines. Furthermore, we determined the glycolytic activity by glucose uptake, lactate secretion assay and ECAR analysis. CCK-8 assay, clone formation assay, flow cytometry and EdU assay were performed to monitor cancer cell proliferation and cell cycle distribution. In addition, nude mice xenograft model was used to investigate the role of PFKFB3 in tumor growth in vivo.Results: In this study, we found that PFKFB3 was significantly up-regulated in RCC tissues and cell lines compared with normal control. Overexpression of PFKFB3 was positively associated with advanced TNM stage and could predict poor prognosis of ccRCC patients. Furthermore, knockdown of PFKFB3 suppresses cell glycolysis, proliferation and cell cycle G1/S transition in RCC cells. Importantly, in vivo experiments confirmed that PFKFB3 knockdown delayed tumor growth derived from the ACHN cell line.Conclusion: Our results suggest that PFKFB3 plays an important role in the progression of RCC via mediating glycolysis and proliferation, and provides a potential therapeutic target for RCC.