Department of Orthopaedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
PLoS One. 2011 Feb 2;6(2):e14648. doi: 10.1371/journal.pone.0014648.
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.
BMI-1 是多梳组基因（PcG）的成员，它与多种恶性肿瘤的发生和发展有关，但它在骨肉瘤中的作用仍需阐明。
方法/主要发现：在本研究中，我们发现 BMI-1 在不同类型的骨肉瘤中过表达。通过慢病毒介导的 RNA 干扰（RNAi）下调 BMI-1 显著抑制骨肉瘤细胞的体外细胞活力和集落形成以及体内致瘤性。BMI-1 敲低通过抑制 PI3K/AKT 通路促进顺铂诱导的细胞凋亡。此外，BMI-1 缺失诱导的表型可以通过强制表达 BMI-1 摆动突变体来挽救，该突变体对小干扰 RNA（siRNA）的抑制具有抗性。
结论/意义：这些发现表明 BMI-1 在骨肉瘤发病机制中起关键作用。
