title: miR-125b develops chemoresistance in Ewing sarcoma/primitive neuroectodermal tumor.
abstract: BACKGROUND
  Diverse functions of microRNAs (miRNAs), including effects on tumorigenesis, proliferation, and differentiation, have been reported, and several miRNAs have also been demonstrated to play an important role in apoptosis. In this study, we investigated the possible role that miRNAs may play in the development of chemoresistance in Ewing sarcoma/primitive neuroectodermal tumor (EWS).
  
  
  METHODS
  We screened doxorubicin (Dox)-resistant EWS cells to identify any distinct miRNA sequences that may regulate the chemoresistance of EWS cells. The effects of miRNAs were evaluated using a chemosensitivity assay. The possible target genes of the miRNAs were predicted using a web-based prediction program.
  
  
  RESULTS
  We found miR-125b to be upregulated in two different Dox-resistant EWS cell lines. The upregulation of miR-125b was also confirmed in the EWS tumors having survived chemotherapy regimen which includes doxorubicin. When miR-125b was knocked down in EWS cells, both the Dox-resistant and parental cells showed an enhanced sensitivity to doxorubicin, which was associated with the upregulation of the pro-apoptotic molecules, p53 and Bak. Inversely, the overexpression of miR-125b in parental EWS cells resulted in enhanced drug resistance, not only to doxorubicin, but also to etoposide and vincristine.
  
  
  CONCLUSIONS
  Our findings suggest that miR-125b may play a role in the development of chemoresistance in EWS by suppressing the expression of the apoptotic mediators, such as p53 and Bak.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Maidashi3-1-1, Fukuoka, 812-8582, Japan. fukushi@med.kyushu-u.ac.jp.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Iida
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Fukushi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujiwara-Okada
authors.forename: Mihoko
authors.initials: M
authors.lastname: Hatano
authors.forename: Akira
authors.initials: A
authors.lastname: Nabashima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kamura
authors.forename: Yukihide
authors.initials: Y
authors.lastname: Iwamoto