Neuroglobin promotes the proliferation and suppresses the apoptosis of glioma cells by activating the PI3K/AKT pathway

Abstract

Our previous study demonstrated that neuroglobin (Ngb) functions as an independent predictive indicator of the prognosis of patients with glioma and promotes cancer cell growth by suppressing apoptosis. However, the understanding of the mechanisms underlying the survival‑enhancing function of Ngb in glioma is limited. In the present study, KEGG PathwayFinder by gene correlation analysis was performed on the R2: Genomics Analysis and Visualization Platform, which revealed a high association between Ngb and the phosphatidylinositol 3‑kinase (PI3K)/AKT pathway using glioma data (GSE4290) from the Gene Expression Omnibus database. Furthermore, western blotting experiments were performed in U251 and U87 glioma cells, and Ngb knockdown using short hairpin RNA reduced the protein levels of phosphorylated (p)‑AKT, p‑mammalian target of rapamycin (mTOR) and antiapoptotic factor Bcl‑2, and increased the expression of the proapoptotic protein Bcl‑2‑associated X, in U251 cells. In addition, Ngb overexpression promoted the activation of the PI3K/AKT pathway in U87 cells. MK2206, a PI3K/AKT signaling inhibitor, reduced the expression of p‑AKT and increased the levels of apoptosis‑associated proteins, including cleaved poly(ADP‑ribose) polymerase 1 and cleaved caspase‑3/7/8, in Ngb‑overexpressing U87 cells. Furthermore, MK2206 treatment reduced the proliferation and induced the apoptosis of Ngb‑overexpressing U87 cells, as indicated by the results of MTT, colony formation and flow cytometry assays. In addition, insulin‑like growth factor‑1, a PI3K/AKT signaling activator, reversed Ngb knockdown‑induced growth arrest and apoptosis in U251 cells. In conclusion, the results of the present study indicate that Ngb may facilitate a malignant phenotype of glioma cells by activating the PI3K/AKT pathway.

Knockdown of BCL6 Inhibited Malignant Phenotype and Enhanced Sensitivity of Glioblastoma Cells to TMZ through AKT Pathway

“…But in U251 cells (one of the p53-mutant cell lines), p53 expression had no significant changes. Besides, some research also showed that several molecules could upregulate BCL2 to inhibit cell apoptosis by AKT and ERK signaling pathways [ 26 , 27 ] which was consistent with our result that knockdown of BCL6 inhibited the AKT and ERK pathways. In addition, BCL2 and Bax are key upstream regulatory factors of caspase cascade which involved in apoptosis [ 28 ], and regulation of BCL2/Bax expression alters proliferation and apoptosis in glioblastoma [ 29 ].…”

Retracted Article: Aclarubicin regulates glioma cell growth and DNA damage through the SIRT1/PI3K/AKT signaling pathway

“…Previous evidences suggest that SIRT1 and PI3K/AKT pathways are important regulators of DNA damage response and cell apoptosis. [23][24][25] Hence, we next examined the molecular mechanisms underlying the role of ACR in glioma cell growth, apoptosis, and DNA damage. Results showed that, compared to control treatment, ACR treatment markedly increased the protein expression of SIRT1 in U87 and U251 cells ( Fig.…”

T-2 Toxin Exposure Induces Apoptosis in TM3 Cells by Inhibiting Mammalian Target of Rapamycin/Serine/Threonine Protein Kinase(mTORC2/AKT) to Promote Ca2+Production

“…Mammalian/mechanistic target of rapamycin (mTOR), a serine/threonine protein kinase (AKT), plays a crucial role in cell growth, proliferation, and apoptosis [ 17 , 18 ]. Recently, it was reported that mTOR could regulate intracellular Ca 2+ in cultured normal podocytes [ 19 , 20 ].…”