Increased expression of ecotropic viral integration site 2A indicates a poor prognosis and promotes osteosarcoma evolution through activating MEK/ERK pathway

J Recept Signal Transduct Res. 2019 Aug;39(4):368-372. doi: 10.1080/10799893.2019.1669182. Epub 2019 Nov 27.

Abstract

Although ecotropic viral integration site 2 A (EVI2A) plays key roles in several cancers, the expression and function of EVI2A in osteosarcoma (OS) have not been investigated. Hence, we explored the expression of EVI2A and its clinical significance of EVI2A of OS. Firstly, we investigated the expression of EVI2A in OS tissues. The relationship of EVI2A expression and survival time was analyzed using Kaplan-Meier plotter. Then, we used quantitative reverse transcription PCR (qRT-PCR) to confirm the expression level of EVI2A in OS cell lines. Cell proliferation, and wound-healing experiments were used to identify the biological function of EVI2A. Moreover, EVI2A-mediated MEK/ERK signaling pathway was evaluated using western blotting. Data suggested that EVI2A was highly expressed in OS tissues, and high-expression of EVI2A was associated with worse overall survival in OS patients. Moreover, the up-regulation of it was observed in OS cell lines (Saos2, and MG63). Knockdown of EVI2A suppressed cell proliferation and migration of OS. Western blotting revealed that the inactivation of MEK/ERK pathway was found in OS cells after EVI2A knockdown. Our data implicated the crucial role of EVI2A in the progression of OS, demonstrating that expression of EVI2A may offer an attractive novel prognostic signature for OS.

Keywords: Osteosarcoma; ecotropic viral integration site 2A; prognosis; proliferation.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology*
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MAP Kinase Kinase 1 / genetics
  • MAP Kinase Kinase 1 / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • Prognosis
  • Signal Transduction
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • EVI2A protein, human
  • Membrane Proteins
  • MAPK1 protein, human
  • MAPK3 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human