Nonstructural maintenance of chromatin condensin I complex subunit G promotes the progression of glioblastoma by facilitating Poly (ADP-ribose) polymerase 1-mediated E2F1 transactivation

Abstract

Abstract Background Nonstructural maintenance of chromatin condensin I complex subunit G (NCAPG), also known as non-structural maintenance of chromosomes condensin I complex subunit G, is mitosis-related protein that widely existed in eukaryotic cells. Increasing evidence has demonstrated that aberrant NCAPG expression was strongly associated with various tumors. However, little is known about the function and mechanism of NCAPG in glioblastoma (GBM). Methods The expression and prognostic value of NCAPG were detected in the clinical databases and tumor samples. The function effects of NCAPG downregulation or overexpression were evaluated in GBM cell proliferation, migration, invasion, and self-renewal in vitro and in tumor growth in vivo. The molecular mechanism of NCAPG was researched. Results We identified that NCAPG was upregulated in GBM and associated with poor prognosis. Loss of NCAPG suppressed the progression of GBM cells in vitro and prolonged survival in mouse models of GBM in vivo. Mechanistically, we revealed that NCAPG positively regulated E2F transcription factor 1 (E2F1) pathway activity. By directly interacting with Poly (ADP-ribose) polymerase 1, a co-activator of E2F1, and facilitating the PARP1-E2F1 interaction to activate E2F1 target gene expression. Intriguingly, we also discovered that NCAPG functioned as a downstream target of E2F1, which was proved by the ChIP and Dual-Luciferase results. Comprehensive data mining and immunocytochemistry analysis revealed that NCAPG expression was positively associated with the PARP1/E2F1 signaling axis. Conclusions Our findings indicate that NCAPG promotes GBM progression by facilitating PARP1-mediated E2F1 transactivation, suggesting that NCAPG is a potential target for anticancer therapy.