Knockdown of NUPR1 inhibits the proliferation of glioblastoma cells via ERK1/2, p38 MAPK and caspase-3

J Neurooncol. 2017 Mar;132(1):15-26. doi: 10.1007/s11060-016-2337-0. Epub 2016 Dec 20.

Abstract

Nuclear protein-1 (NUPR1), located on chromosome 16p11.2, is a stress response factor that plays an important role in the growth and migration of human malignant tumor cells. However, the role of NUPR1 in glioblastoma remains poorly understood. The expression level of NUPR1 was detected by quantitative real-time PCR and immunohistochemistry (IHC). Wound healing, MTT, cell counting and BrdU assays were used to analyze the migration and proliferation of glioblastoma cells after down-regulating NUPR1 expression using a lentiviral vector. FACS analysis and a signaling antibody array kit were used to detect the mechanism by which NUPR1 modulates cell cycle and apoptosis activities in glioblastoma cells. We confirmed that NUPR1 was up-regulated in glioblastoma tissues compared to NB tissues. Down-regulation of NUPR1 suppressed cell migration and proliferation, arrested the cell cycle in the G0/G1 phase and promoted apoptosis in U251 and U87 cells in vitro. Furthermore, the expression levels of phosphorylated ERK1/2, p38 MAPK and cleaved caspase-3 were decreased upon silencing NUPR1 expression in U251 and U87 cells. In summary, NUPR1 plays an important role in the growth and migration of human glioblastoma cells. Knockdown of NUPR1 suppressed glioblastoma cell growth by arresting the cell cycle and inducing cell apoptosis via decreases in the expression of ERK1/2, p38 MAPK and caspase-3.

Keywords: Apoptosis; Globlastoma; Migration; NUPR1; Proliferation.

MeSH terms

  • Apoptosis
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Caspase 3*
  • Cell Cycle Checkpoints
  • Cell Movement
  • Cell Proliferation*
  • Down-Regulation
  • Female
  • Gene Knockdown Techniques
  • Glioblastoma / metabolism*
  • Humans
  • MAP Kinase Signaling System*
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Tumor Cells, Cultured
  • Wound Healing

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • NUPR1 protein, human
  • Neoplasm Proteins
  • Caspase 3