Overexpression of BMI-1 promotes cell growth and resistance to cisplatin treatment in osteosarcoma

PLoS One. 2011 Feb 2;6(2):e14648. doi: 10.1371/journal.pone.0014648.

Abstract

Background: BMI-1 is a member of the polycomb group of genes (PcGs), and it has been implicated in the development and progression of several malignancies, but its role in osteosarcoma remains to be elucidated.

Methodology/principal findings: In the present study, we found that BMI-1 was overexpressed in different types of osteosarcomas. Downregulation of BMI-1 by lentivirus mediated RNA interference (RNAi) significantly impaired cell viability and colony formation in vitro and tumorigenesis in vivo of osteosarcoma cells. BMI-1 knockdown sensitized cells to cisplatin-induced apoptosis through inhibition of PI3K/AKT pathway. Moreover, BMI-1-depletion-induced phenotype could be rescued by forced expression of BMI-1 wobble mutant which is resistant to inhibition by the small interfering RNA (siRNA).

Conclusions/significance: These findings suggest a crucial role for BMI-1 in osteosarcoma pathogenesis.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Cell Proliferation* / drug effects
  • Cells, Cultured
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use*
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Mice, Transgenic
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Osteosarcoma / drug therapy
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • Polycomb Repressive Complex 1
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / physiology*
  • RNA, Small Interfering / pharmacology
  • RNA, Small Interfering / therapeutic use
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Repressor Proteins / physiology*
  • Up-Regulation / genetics
  • Up-Regulation / physiology

Substances

  • Antineoplastic Agents
  • Bmi1 protein, mouse
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Repressor Proteins
  • Polycomb Repressive Complex 1
  • Cisplatin