Abstract

Diffuse large B-cell lymphoma (DLBCL) represents the most prevalent form of non-Hodgkin lymphoma, distinguished by its aggressive clinical presentation and poor patient outcomes. This study investigated the role of nuclear receptor subfamily 2 group F member 2 (NR2F2) and 14-3-3 epsilon (YWHAE) in DLBCL progression. NR2F2 and YWHAE were highly expressed in DLBCL cell lines and tumor tissues of patients with DLBCL. Elevated expression of both genes correlated with advanced Ann Arbor stage and higher International Prognostic Index scores in DLBCL patients. Functional assays demonstrated that knockdown of NR2F2 or YWHAE suppressed DLBCL cell proliferation, migration, and invasion, as well as tumor growth in xenograft models. Mechanistically, NR2F2 transcriptionally activated YWHAE by binding to its promoter, thereby promoting phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling. Notably, treatment with a PI3K activator in YWHAE-silenced cells, or YWHAE overexpression in NR2F2-silenced cells, partially reversed the inhibitory effects on malignant behaviors of DLBCL cells. Collectively, these findings indicate that NR2F2 promotes DLBCL progression through transcriptional activation of YWHAE and subsequent activation of the PI3K/AKT pathway, suggesting a potential therapeutic target for DLBCL.