Downregulation of BZW2 inhibits osteosarcoma cell growth by inactivating the Akt/mTOR signaling pathway

Oncol Rep. 2017 Oct;38(4):2116-2122. doi: 10.3892/or.2017.5890. Epub 2017 Aug 8.

Abstract

Osteosarcoma is the most common malignant bone tumor in adolescents. The function of basic leucine zipper and W2 domains 2 (BZW2) in tumor progression has been reported. However, the role and mechanisms of BZW2 in osteosarcoma remain to be determined. The aim of the present study was to reveal the expression and biological functions of BZW2 in osteosarcoma and to elucidate the proximal mechanisms underlying these functions. The expression of BZW2 in osteosarcoma tissues and cell lines was assessed by qRT-PCR, western blotting and immunohistochemistry. BZW2 overexpression was detected in osteosarcoma cell lines. Clinically, BZW2 expression was higher in osteosarcoma tissues than in corresponding non-tumor tissues and was associated with advanced Enneking stage and tumor recurrence. The knockdown of BZW2 using siRNA inhibited osteosarcoma cell proliferation, colony-forming ability, and the cell cycle at the G2/M phase in vitro. Host signaling pathways affected by BZW2 were detected using a PathScan Intracellular Signaling Antibody Array kit. These data demonstrated that the knockdown of BZW2 suppresses protein phosphorylation in the Akt/mTOR signaling pathway. These observations suggest that BZW2 is upregulated and has a pro-tumor effect in osteosarcoma via activation of the Akt/mTOR signaling pathway and thus is a potential target for gene therapy.

MeSH terms

  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / therapeutic use
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Molecular Targeted Therapy
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology
  • Proto-Oncogene Proteins c-akt / genetics*
  • Signal Transduction / genetics
  • Stem Cells / metabolism
  • Stem Cells / pathology
  • TOR Serine-Threonine Kinases / genetics*

Substances

  • BZW2 protein, human
  • DNA-Binding Proteins
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt