Circular RNA Dipeptidyl Peptidase 4 (circDPP4) Stimulates the Expression of Glutamate Dehydrogenase 1 to Contribute to the Malignant Phenotypes of Prostate Cancer by Sponging miR-497-5p

Abstract

Circular RNA dipeptidyl peptidase 4 (circDPP4) has been confirmed as a novel oncogene in prostate cancer (PCa). In this study, we aimed to explore the underlying mechanism of circDPP4 in PCa progression. Levels of circDPP4, microRNA (miR)-497-5p, glutamate dehydrogenase 1 (GLUD1), proliferating cell nuclear antigen (PCNA), BCL2 associated X, apoptosis regulator (Bax), E-cadherin and Ki67 were gauged by a quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, or immunohistochemical method. We assessed the roles of variables in PCa cell phenotypes by measuring cell growth, apoptosis, motility and invasiveness. We performed RNA immunoprecipitation (RIP) and dual-luciferase reporter assays to confirm the interactions of circDPP4/miR-497-5p and miR-497-5p/GLUD1. A xenograft model was established to gauge the effect of circDPP4 in the tumorigenicity of PCa cells. PCa tumor tissues and cell lines revealed higher levels of circDPP4 and GLUD1 and a lower expression of miR-497-5p than controls. CircDPP4 silencing hindered the growth, motility and invasiveness of PCa cells. Conversely, silencing circDPP4 enhanced PCa cell apoptosis. Mechanistic analysis showed that circDPP4 functioned as a miR-497-5p sponge to reduce the suppressive action of miR-497-5p on GLUD1, which was validated as a direct miR-497-5p target. Furthermore, circDPP4 knockdown weakened the tumorigenicity of PCa cells. CircDPP4 facilitated PCa process by mediating the miR-497-5p/GLUD1 axis, providing a possible therapy target for PCa.

Keywords: GLUD1; Prostate cancer; circDPP4; miR-497-5p.