miR-125b develops chemoresistance in Ewing sarcoma/primitive neuroectodermal tumor.
miR-125b develops chemoresistance in Ewing sarcoma/primitive neuroectodermal tumor.
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DOI：
10.1186/1475-2867-13-21
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发表时间：
2013-03-04
影响因子：
5.8
通讯作者：
Iwamoto Y
中科院分区：
文献类型：
--
作者：
Iida K;Fukushi J;Matsumoto Y;Oda Y;Takahashi Y;Fujiwara T;Fujiwara-Okada Y;Hatano M;Nabashima A;Kamura S;Iwamoto Y
已经报道了microRNA（miRNAs）的多种功能，包括对肿瘤发生、增殖和分化的影响，并且一些miRNAs也已被证明在细胞凋亡中起重要作用。在这项研究中，我们研究了miRNA可能在尤文肉瘤/原始神经外胚层肿瘤（EWS）化疗耐药的发展中发挥的作用。我们筛选了阿霉素（Dox）耐药的EWS细胞，以确定任何不同的miRNA序列，可能会调节EWS细胞的耐药性。使用化学敏感性测定来评估miRNA的作用。使用基于网络的预测程序预测miRNA的可能靶基因。我们发现miR-125 b在两种不同的Dox耐药EWS细胞系中上调。miR-125 b的上调也在具有存活的化疗方案（包括多柔比星）的EWS肿瘤中得到证实。当miR-125 b在EWS细胞中被敲低时，Dox抗性细胞和亲本细胞均显示出对阿霉素的敏感性增强，这与促凋亡分子p53和巴克的上调有关。然而，在亲本EWS细胞中miR-125 b的过表达导致不仅对多柔比星，而且对依托泊苷和长春新碱的耐药性增强。我们的研究结果表明，miR-125 b可能通过抑制细胞凋亡介质如p53和巴克的表达，在EWS的化疗耐药性的发展中发挥作用。
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). 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. 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. 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.
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影响因子：
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作者：
Li, Yan;Tanaka, Kazuhiro;Iwamoto, Yukihide
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影响因子：
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作者：
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通讯作者：
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