HOXA5 overexpression promotes osteosarcoma cell apoptosis through the p53 and p38α MAPK pathway

Gene. 2019 Mar 20:689:18-23. doi: 10.1016/j.gene.2018.11.081. Epub 2018 Dec 3.

Abstract

Osteosarcoma is the most common malignant bone tumor in children and adolescents. Aberrant expression of HOXA5 results in various diseases, including cancers. However, the specific function and molecular mechanism of HOXA5 in osteosarcoma is not fully understood. In the present study, we focused on HOXA5 in U2OS and MG63 cells in vitro. We observed lower expression of HOXA5 in U2OS, MG63, and SaOS2 human osteosarcoma cells, compared with hFOB1.19 human osteoblastic cells. HOXA5 overexpression in U2OS and MG63 cells markedly reduced cell survival and proliferation and elevated cell apoptosis and caspase-3 activity. HOXA5 also activated the p38α MAPK pathway by increasing p53. Treating U2OS and MG63 cells with the p53 inhibitor α-pifithrin or the p38α MAPK inhibitor SB203580 led to higher cell survival and proliferation and lower cell apoptosis, compared with the pcDNA3.1-HOXA5 group. In conclusion, our study showed that the p53 and p38α MAPK signal axis facilitated HOXA5's role in inhibiting growth and stimulating apoptosis of osteosarcoma cells.

Keywords: HOXA5; Osteosarcoma; p38α MAPK; p53.

MeSH terms

  • Apoptosis / genetics*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / genetics*
  • Humans
  • MAP Kinase Signaling System / physiology
  • Mitogen-Activated Protein Kinase 14 / genetics
  • Mitogen-Activated Protein Kinase 14 / metabolism
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology*
  • Tumor Suppressor Protein p53 / genetics
  • Up-Regulation / genetics

Substances

  • HOXA5 protein, human
  • Homeodomain Proteins
  • Tumor Suppressor Protein p53
  • Mitogen-Activated Protein Kinase 14