title: Overexpression of BMI-1 promotes cell growth and resistance to cisplatin treatment in osteosarcoma.
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.
  
  
  RESULTS
  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
  These findings suggest a crucial role for BMI-1 in osteosarcoma pathogenesis.
authors.affiliation: Department of Orthopaedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wu
authors.forename: Li
authors.initials: L
authors.lastname: Min
authors.forename: Dafu
authors.initials: D
authors.lastname: Chen
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Hao
authors.forename: Yuanhui
authors.initials: Y
authors.lastname: Duan
authors.forename: Guixing
authors.initials: G
authors.lastname: Qiu
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology / Q000627:therapeutic use; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; C489421:Bmi1 protein, mouse; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1; D002945:Cisplatin