NLGN3 promotes neuroblastoma cell proliferation and growth through activating PI3K/AKT pathway

Eur J Pharmacol. 2019 Aug 15:857:172423. doi: 10.1016/j.ejphar.2019.172423. Epub 2019 May 28.

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.

Keywords: NLGN3; Neuroblastoma; PI3K/AKT; Tumor growth.

MeSH terms

  • Apoptosis
  • Cell Adhesion Molecules, Neuronal / deficiency
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuroblastoma / pathology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction*

Substances

  • Cell Adhesion Molecules, Neuronal
  • Membrane Proteins
  • Nerve Tissue Proteins
  • neuroligin 3
  • Proto-Oncogene Proteins c-akt