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

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.

Sanggenon C inhibits cell proliferation and induces apoptosis by regulating the MIB1/DAPK1 axis in glioblastoma.

Sanggenon C (SC), a herbal flavonoid extracted from Cortex Mori, has been mentioned to possess more than one treasured organic properties. However, the molecular mechanism of its anti-tumor impact in glioblastoma (GBM) remains unclear. In this study, we reported that SC displayed a GBM-suppressing impact in vitro and in vivo with no apparent organ toxicity. SC dramatically suppressed cell proliferation-induced cell apoptosis in GBM cells. Mechanistically, we unveiled that SC modulated the protein expression of death associated protain kinase 1 (DAPK1) by controlling the ubiquitination and degradation of DAPK1. Quantitative proteomic and Western blot analyses showed that SC improved DAPK1 protein degradation via decreasing the expression of E3 ubiquitin ligase Mindbomb 1 (MIB1). More importantly, the effects of SC on cell proliferation and apoptosis of GBM cells have been in part reversed through DAPK1 downregulation or MIB1 overexpression, respectively. These results indicated that SC might suppress cell proliferation and induce cell apoptosis by decreasing MIB1-mediated DAPK1 degradation. Furthermore, we found that SC acted synergistically with temozolomide (TMZ), an anti-cancer drug used in GBM, resulting in elevated chemotherapeutic sensitivity of GBM to TMZ. Collectively, our data suggest that SC might be a promising anti-cancer agent for GBM therapy.