Suppression of PTTG1 inhibits cell angiogenesis, migration and invasion in glioma cells

Med Oncol. 2020 Jul 28;37(8):73. doi: 10.1007/s12032-020-01398-2.

Abstract

Pituitary tumor-transforming gene 1 (PTTG1) has been identified as an oncogene and is overexpressed in many tumor types. However, the role of PTTG1 in glioblastoma (GBM) has not been well characterized, especially in relation to angiogenesis, migration, and invasion. In the present study, our results showed that the expression of PTTG1 was significantly higher in patients with GBM. Bioinformatic analysis showed that angiogenesis and the cell migration-related process were increased in patients with high PTTG1 expression levels; meanwhile, PTTG1 was positively correlated with marker genes of angiogenesis, migration and the evasion of apoptosis. In vitro assays showed that PTTG1 knockdown dramatically suppressed angiogenesis, migration and invasion, and increased the apoptosis of GBM cells. Moreover, our results also showed that silencing PTTG1 suppressed the activity of the TGF-β/PI3K-AKT-mTOR pathway, which induced tumor deterioration in multiple organs. Overall, our findings indicate that PTTG1 is a glioma malignant factor that promotes angiogenesis, migration, invasion, and the evasion of apoptosis, and these roles may be related to the TGF-β/PI3K-AKT-mTOR pathway. Thus, the targeted inhibition of PTTG1 might be a novel therapeutic strategy and a potential diagnostic biomarker for GBM-targeted therapies.

Keywords: Angiogenesis; Glioblastoma; Invasion; Pituitary tumor-transforming gene 1.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Computational Biology / methods
  • Databases, Genetic
  • Glioma / blood supply*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / prevention & control
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics
  • Securin / antagonists & inhibitors*
  • Securin / genetics
  • Securin / metabolism
  • Signal Transduction
  • Survival Rate
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • RNA, Small Interfering
  • Securin
  • pituitary tumor-transforming protein 1, human
  • MTOR protein, human
  • TOR Serine-Threonine Kinases