COP1 facilitates the proliferation, invasion, and migration of glioma cells by ubiquitination of DLG3 protein

Abstract

ABSTRACT Objective Glioma is a heterogeneous group of brain tumors that remains largely incurable. Constitutive photomorphogenic 1 (COP1) acts as an E3 ligase for tumor regulation. This study explored the mechanism of COP1 in glioma cell proliferation, invasion, and migration. Methods COP1 and discs large homolog 3 (DLG3) expressions in glioma cells were determined using RT-qPCR or Western blotting, followed by transfection of si-COP1 or si-DLG3 into LN229 cells. Glioma cell proliferation, invasion, and migration were measured using CCK-8, EdU staining, and Transwell assays. The binding of COP1 and DLG3 was verified using co-immunoprecipitation. The ubiquitination level of DLG3 protein was tested after MG132 treatment. Functional rescue experiments were performed to validate the role of DLG3 in the regulation of glioma cells by COP1. Results COP1 was highly expressed in glioma cells. COP1 silencing repressed glioma cell proliferation, invasion, and migration. COP1 bound to DLG3 protein and enhanced the ubiquitination of DLG3. DLG3 silencing reversed the inhibitory effect of COP1 silencing on glioma cell proliferation, invasion, and migration. Conclusion COP1 facilitated the proliferation, invasion, and migration of glioma cells by ubiquitination of DLG3 protein.