miR-125b develops chemoresistance in Ewing sarcoma-primitive neuroectodermal tumorReportar como inadecuado




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Cancer Cell International

, 13:21

First Online: 04 March 2013Received: 10 October 2012Accepted: 28 February 2013

Abstract

BackgroundDiverse 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.

MethodsWe 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.

ResultsWe 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.

ConclusionsOur 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.

KeywordsEwing sarcoma-primitive neuroectodermal tumor miR-125b p53 Bak Chemoresistance AbbreviationsmiRNAmicroRNA

EWSEwing sarcoma-primitive neuroectodermal tumor

DoxDoxorubicin

P-gpP-glycoprotein

GAPDHGlyceraldehyde 3-phosphate dehydrogenase

FFPEFormalin-fixed, paraffin-embedded

Electronic supplementary materialThe online version of this article doi:10.1186-1475-2867-13-21 contains supplementary material, which is available to authorized users.

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Autor: Keiichiro Iida - Jun-ichi Fukushi - Yoshihiro Matsumoto - Yoshinao Oda - Yusuke Takahashi - Toshifumi Fujiwara - Yuko Fujiw

Fuente: https://link.springer.com/







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