Neuropilin and tolloid-like 2 regulates the progression of osteosarcoma

Gene. 2021 Feb 5:768:145292. doi: 10.1016/j.gene.2020.145292. Epub 2020 Nov 4.

Abstract

Neuropilin and tolloid-like 2 (NETO2) is aberrantly expressed in various malignancies. However, its role in osteosarcoma (OS) remains to be elucidated. This study aimed to identify the function of NETO2 in OS cells. The expression of NETO2 in sarcoma tissues was determined using the GEPIA database, and the mRNA and protein expression of NETO2 in OS cells and OS tissue was also assessed. The biological effects of NETO2 on OS cells were determined by overexpressing and downregulating NETO2. Cell proliferation, invasion, migration, colony formation, and epithelial-mesenchymal transition in OS cells were evaluated. Consistent with the GEPIA database, expression of NETO2 was upregulated in human OS samples and cell lines. NETO2 overexpression not only promoted the proliferation, colony formation, invasion, and epithelial-mesenchymal transition of OS cells, but also activated the PI3K/AKT signaling. NETO2 downregulation resulted in opposite effects. Furthermore, after using an AKT inhibitor, the effects of NETO2 on OS cells were attenuated. In conclusion, this study showed that NETO2 functions as an oncogene of osteosarcomas by activating the PI3K/AKT pathway.

Keywords: NETO2; Osteosarcoma; PI3K/AKT.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Disease Progression
  • Down-Regulation / physiology
  • Epithelial-Mesenchymal Transition / physiology
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Membrane Proteins / metabolism*
  • MicroRNAs / metabolism
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / physiology
  • Up-Regulation / physiology

Substances

  • Membrane Proteins
  • MicroRNAs
  • NETO2 protein, human
  • Proto-Oncogene Proteins c-akt