Overexpression of BMI-1 promotes cell growth and resistance to cisplatin treatment in osteosarcoma.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 21311599.
- Also identified by DOI 10.1371/journal.pone.0014648 and PMC identifier 3032734.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Bone Neoplasms
- Cell Proliferation
- Cisplatin
- Drug Resistance, Neoplasm
- Nuclear Proteins
- Osteosarcoma
- Proto-Oncogene Proteins
- Repressor Proteins