Prognosis-related VDAC1 regulates the proliferation and apoptosis of osteosarcoma cells via the MAPK signaling pathway

Genomics. 2023 May;115(3):110595. doi: 10.1016/j.ygeno.2023.110595. Epub 2023 Mar 5.

Abstract

The role of VDAC1 in osteosarcoma is unclear. We explored the effect of VDAC1 on osteosarcoma development by combining bioinformatic analysis and experimental identification. This study suggested that VDAC1 is an independent prognostic factor for osteosarcoma. Patients with high VDAC1 expression have a poor survival rate. VDAC1 was overexpressed in osteosarcoma cells. After silencing VDAC1, the proliferation of osteosarcoma cells decreased, and the apoptosis rate increased. Gene set variation analysis and gene set enrichment analysis indicated that VDAC1 was associated with the MAPK signaling pathway. After VDAC1 siRNA, SB203580 (a p38 inhibitor), SP600125 (a JNK inhibitor) and α-pifithrin (a p53 inhibitor) treatment, the proliferative capacity was weaker in the si-VDAC1 group than in the si-VDAC1 + SB203580, si-VDAC1 + SP600125, and si-VDAC1 + α-pifithrin groups. In conclusion, prognosis-related VDAC1 can affect osteosarcoma cells' proliferative activity and apoptosis level. The MAPK signaling pathway mediates VDAC1 regulation of osteosarcoma cell development.

Keywords: MAPK signaling pathway; Osteosarcoma; Prognosis; VDAC1.

MeSH terms

  • Apoptosis / genetics
  • Bone Neoplasms* / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • Osteosarcoma* / genetics
  • Prognosis
  • Signal Transduction
  • Voltage-Dependent Anion Channel 1 / metabolism

Substances

  • pyrazolanthrone
  • pifithrin
  • VDAC1 protein, human
  • Voltage-Dependent Anion Channel 1