ABSTRACT
Neuroblastoma is the most common extracranial solid tumor of childhood, previous studies show synaptic protein neuroligin-3 (NLGN3) promotes glioma proliferation and growth, However, no investigation about the role of NLGN3 in neuroblastoma was reported. Here, we found NGLGN3 was significantly upregulated in neuroblastoma cells and tissues, its overexpression significantly promoted neuroblastoma cell proliferation and growth determined by MTT analysis, colony formation assay, cell cycle progression analysis, BrdU incorporation assay and animal model, while its knockdown inhibited cell proliferation and growth. Then we found NLGN3 could increase the phosphorylation level of AKT and the transcription activity of FOXO family, suggesting NLGN3 activated PI3K/AKT pathway, inhibition of PI3K/AKT pathway in NLGN3 overexpressing cells inhibited cell proliferation, confirming NLGN3 promoted neuroblastoma proliferation through activating PI3K/AKT pathway. In summary, we found NLGN3 promoted neuroblastoma cell proliferation and growth through activating PI3K/AKT pathway and providing a new target for neuroblastoma therapy.
Subject(s)
Cell Adhesion Molecules, Neuronal/metabolism , Membrane Proteins/metabolism , Nerve Tissue Proteins/metabolism , Neuroblastoma/pathology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Apoptosis , Cell Adhesion Molecules, Neuronal/deficiency , Cell Adhesion Molecules, Neuronal/genetics , Cell Line, Tumor , Cell Proliferation , Disease Progression , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Membrane Proteins/deficiency , Membrane Proteins/genetics , Nerve Tissue Proteins/deficiency , Nerve Tissue Proteins/genetics , PhosphorylationABSTRACT
Neuroblastoma is a childhood tumor, and high-stage neuroblastoma has a poor prognosis. The regulatory mechanisms for neuroblastoma progression are poorly understood. In present study, we found that GDNF family receptor alpha 2 (GFRA2) was upregulated in neuroblastoma cells and tissues, and its overexpression promoted neuroblastoma cell proliferation, as revealed using colony formation, soft agar growth, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays Tumor suppressor phosphatase and tensin homolog (PTEN) is an inhibitor of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) pathway that interacts with GFRA2. A luciferase activity assay showed GFRA2 inhibits the transcriptional activity of the forkhead box O (FOXO) family proteins, which suggested that GFRA2 activated the PI3K/AKT pathway. Inhibition of the PI3K/AKT pathway in GFRA2 overexpressing cells decreased cell proliferation, confirming that GFRA2 promoted neuroblastoma cell proliferation by activating the PI3K/AKT pathway. In summary, cell proliferation via the GFRA2-PTEN-PI3K/AKT axis may represent new target to develop treatments for neuroblastoma.
