TRIML2 Promotes Bladder Cancer Progression via the ZFP42/IGF2BP1-Mediated Glycolytic Pathway

BackgroundBladder cancer (BLCA) remains a prevalent and lethal malignancy with limited therapeutic options and poor prognosis, particularly in muscle-invasive cases. The molecular mechanisms underlying BLCA progression and metabolic reprogramming are not fully understood.Materials and MethodsComprehensive bioinformatics analyses and experimental validation were performed to identify and characterize the role of Tripartite Motif-Like 2 (TRIML2) in BLCA. Expression patterns were assessed in BLCA tissues, followed by in vitro assays to evaluate proliferation, migration, glycolysis, and apoptosis. Mechanistic studies investigated the interaction between TRIML2 and ZFP42, and its effect on IGF2BP1 transcription and glycolytic enzyme regulation. In vivo xenograft models were established to further assess the impact of TRIML2 knockdown on tumor growth and glycolysis.ResultsTRIML2 was significantly upregulated in BLCA tissues, and its high expression correlated with advanced tumor grade, stage, and poor survival. Functional assays demonstrated that TRIML2 promoted BLCA cell proliferation, migration, and glycolysis while inhibiting apoptosis. Mechanistically, TRIML2 interacted with ZFP42 to enhance IGF2BP1 transcription, thereby upregulating glycolytic enzymes including PKM2, LDHA, HK2, and GLUT1. This axis increased glucose uptake, ATP production, and tumor growth. In vivo studies confirmed that TRIML2 knockdown suppressed BLCA progression and glycolysis in xenograft models.ConclusionOur findings identify TRIML2 as a novel oncogenic driver in BLCA that promotes metabolic reprogramming through the TRIML2/ZFP42/IGF2BP1 axis. Targeting this pathway may provide a promising therapeutic strategy for BLCA.