Non-SMC Condensin I Complex Subunit G (NCAPG) Drives the Malignant Phenotypes of Glioblastoma Cells via Activation of Phosphoinositide 3-Kinase/Protein Kinase B (PI3K/AKT) Pathway

Abstract

Background: Since non-SMC condensin I complex subunit G (NCAPG) was implicated in glioblastoma (GBM), the aim of our study is to further elucidate the underlying mechanism. Methods: The data on NCAPG expression in GBM were retrieved using bioinformatics. The assays of cell counting kit-8, scratch, transwell, tube formation, and flow cytometry were conducted to test the malignant phenotypes of GBM cells. An intradermal angiogenesis assay was additionally performed using male BALB/c nude mice to quantify new blood capillaries and to determine the formation of vessel wall. Western blot was used to detect proteins related to Phosphatidylinositol 3-Kinases/Protein Kinase B (PI3K/AKT) signaling pathway, fas-associated protein with death domain (FADD), and caspase 8/9 expression. Both quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect NCAPG, Cyclin D1, vascular endothelial growth factor (VEGF), B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X (Bax) expression. Results: NCAPG exhibited a high expression pattern in GBM. Overexpressed NCAPG drove the malignant phenotypes in vitro and angiogenesis in vivo. This was accompanied by increased Cyclin D1, Bcl-2, VEGF, procaspase-8/9, phosphorylation (p) of PI3K, and phosphorylated-Protein Kinase B (p-AKT) levels, while concurrently diminishing the Bax, cleaved caspase-3 and p-forkhead box O4 (FOXO4). In contrast, silencing the NCAPG produced opposite results. Further, the effects of NCAPG overexpression and knockdown were reversed by PI3K/AKT suppressor LY294002 and activator insulin-like growth factor 1 (IGF-1) (p < 0.01), respectively. Conclusions: NCAPG plays an oncogenic role in GBM, and its silencing presents a potentially therapeutic option for patients with GBM.