circDHX33 suppresses glycolysis, malignant proliferation, and metastasis in prostate cancer by interacting with RNA-binding protein IGF2BP2 to destabilize its protein.

Abstract

Prostate cancer (PCa) is a malignant tumor characterized by dependence on androgens and enhanced glycolytic processes in response to the energy demands of rapid proliferation. This study delved into the role of circDHX33 interacting with IGF2BP2 in regulating the malignant behavior of PCa. circRNA expression data from PCa tissues and normal tissues were selected from the GEO database, and differentially expressed circRNAs were screened out. circDHX33 expression in clinical PCa samples was verified by RT-qPCR. Cellular experiments included cell culture, RNA interference and overexpression assays, as well as the use of Transwell migration invasion assay and EdU cell proliferation assay to assess the effect of circDHX33 on the proliferation and migration of PC-3 cells. In addition, its regulatory effect on energy metabolism in tumor cells was assessed by glycolysis assay. FISH assay, RNA pull-down, silver staining assay, and RIP were used to evaluate the interaction between circDHX33 and IGF2BP2. circDHX33 expression was significantly reduced in PCa tissues relative to normal tissues. Overexpression of circDHX33 significantly inhibited the glycolytic activity, proliferative capacity, and migratory and invasive abilities of PC-3 cells, and this effect was closely related to its reduction of IGF2BP2 protein stability. Knockdown of IGF2BP2 could reverse the malignant behavior of cells enhanced by circDHX33 knockdown. In addition, the direct intracellular interaction between circDHX33 and IGF2BP2 was verified. circDHX33 inhibits glycolysis and malignant proliferation in PCa through interaction with IGF2BP2, suggesting its potential as a potential therapeutic target.