TRIM28 facilitates diffuse large B-cell lymphoma progression by inducing glycolytic reprogramming through the E2F1/PKM2 axis.

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignancy in which metabolic adaptation contributes to aggressive behavior and treatment resistance. Although TRIM28 has been implicated in several cancers, its role in DLBCL remains unclear. Here, we investigated the function of TRIM28 in DLBCL progression and glycolytic reprogramming. TRIM28 expression was elevated in the TCGA DLBC cohort and in DLBCL cell lines compared with the normal B-cell line GM12878, and it was positively correlated with PKM2 expression in GEPIA. Gain- and loss-of-function assays showed that TRIM28 promoted cell proliferation and migration while suppressing apoptosis. Metabolic analyses further demonstrated that TRIM28 increased extracellular acidification, ATP production, lactate generation, and the expression of glycolysis-related genes, including PFKFB3, HK2, and PKM2. Mechanistically, bioinformatic analysis and dual-luciferase reporter assays identified PKM2 as a transcriptional target of E2F1, and TRIM28 upregulated E2F1 at both mRNA and protein levels, suggesting that TRIM28 acts upstream of the E2F1/PKM2 axis. Importantly, silencing either E2F1 or PKM2 markedly attenuated the effects of TRIM28 on DLBCL cell growth, migration, and glycolytic activity. In a xenograft model, TRIM28 overexpression accelerated tumor growth, whereas E2F1 or PKM2 knockdown significantly reversed these effects. Collectively, TRIM28 facilitates DLBCL progression by inducing glycolytic reprogramming through the E2F1/PKM2 axis, highlighting a potential therapeutic target.