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Cancer Cell International
Published in: Cancer Cell International 1/2013

Open Access 01-12-2013 | Primary research

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

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

Published in: Cancer Cell International | Issue 1/2013

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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.
Appendix
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Metadata
Title
miR-125b develops chemoresistance in Ewing sarcoma/primitive neuroectodermal tumor
Authors
Keiichiro Iida
Jun-ichi Fukushi
Yoshihiro Matsumoto
Yoshinao Oda
Yusuke Takahashi
Toshifumi Fujiwara
Yuko Fujiwara-Okada
Mihoko Hatano
Akira Nabashima
Satoshi Kamura
Yukihide Iwamoto
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2013
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-13-21

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