PUM2 Promotes Aerobic Glycolysis and Tumor Progression in Diffuse Large B-Cell Lymphoma Cells by Mediating the Stability of CBX3

Abstract

Background: In recent years, there has been a growing interest in understanding the role of RNA binding proteins (RBPs), such as pumilio homolog 2 (PUM2), in the development of diffuse large B-cell lymphoma (DLBCL). Despite this attention, the precise contribution of PUM2 in the progression of DLBCL has not been fully elucidated. This study aimed to examine the role of PUM2 in the development of DLBCL. Methods: To determine the expression level and prognostic value of PUM2 in DLBCL, we employed quantitative real-time polymerase chain reaction (qRT-PCR) analysis, immunoblotting, and immunohistochemical (IHC) staining techniques. Moreover, we examined the impact of PUM2 on DLBCL cell proliferation and glucose metabolism through PUM2 overexpression or silencing. In vivo studies were conducted to evaluate the effect of PUM2 on tumor growth post-transplantation. Furthermore, we utilized luciferase reporter assays, RNA immunoprecipitation (RIP), and RNA pull-down experiments to elucidate the molecular mechanism by which PUM2 regulates chromobox protein homolog 3 (CBX3) expression via its 3′UTR. Results: Our research revealed that PUM2 was upregulated in clinical samples and DLBCL cell lines (p < 0.001). Additionally, ectopic expression of PUM2 enhanced the proliferation and aerobic glycolysis of DLBCL cells, and this effect was inhibited by silencing PUM2 (p < 0.05). Moreover, PUM2 directly bound to the 3′UTR of CBX3 mRNA and increased its stability. Consequently, PUM2 interacted with and stabilized CBX3 mRNA, thereby promoting the proliferation and glycolytic metabolism of DLBCL cells. Conclusions: PUM2 might be a novel regulator of glucose metabolism in DLBCL cells by modulating CBX3 mRNA stability.