MiR-125b develops chemoresistance in Ewing sarcoma/primitive neuroectodermal tumor

Keiichiro Iida, Jun-Ichi Fukushi, Yoshihiro Matsumoto, Yoshinao Oda, Yusuke Takahashi, Toshifumi Fujiwara, Yuko Fujiwara-Okada, Mihoko Hatano, Akira Nabashima, Satoshi Kamura, Yukihide Iwamoto

研究成果: Contribution to journalArticle査読

51 被引用数 (Scopus)

抄録

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.

本文言語英語
論文番号21
ジャーナルCancer Cell International
13
1
DOI
出版ステータス出版済み - 3 4 2013

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 遺伝学
  • 癌研究

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