...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Oncogene >MiR-30a-5p connects EWS-FLI1 and CD99, two major therapeutic targets in Ewing tumor
【24h】

MiR-30a-5p connects EWS-FLI1 and CD99, two major therapeutic targets in Ewing tumor

机译：MiR-30a-5p连接Ewing肿瘤中的两个主要治疗靶点EWS-FLI1和CD99

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Ewing sarcoma is a pediatric bone tumor characterized in 85% of cases by the fusion between EWS and FLI1 genes that results in the expression of the EWS-FLI1 aberrant transcription factor. Histologically, the Ewing tumor expresses high levels of the CD99 membrane glycoprotein. It has been recently described that CD99 expression contributes to the Ewing tumor oncogenesis by modulating growth and differentiation of tumor cells. Different studies have also shown that overexpression of EWS-FLI1 induces CD99 expression in non-Ewing cells. At the opposite, the knockdown of EWS-FLI1 expression by siRNA approaches has no significant effect on CD99 mRNA level in Ewing cells. Here, by in vivo and in vitro studies, we show that while EWS-FLI1 inhibition has only slight effects on the amount of CD99 transcript, it induces a dramatic decrease of the CD99 protein expression level, hence suggesting post-transcriptional regulations, possibly mediated by microRNAs. To further investigate this issue, we identified a set of 91 miRNAs that demonstrate EWS-FLI1 modulation, three of them being predicted to bind CD99 3鈥?untranslated region (3鈥睻TR). Among these, we show that miR-30a-5p has the ability to interact with the 3鈥睻TR region of CD99 and to regulate its expression. Moreover, the re-expression of miRNA-30a-5p in Ewing cell line induces decreased cell proliferation and invasion. In this study, we therefore show that miR-30a-5p constitutes a major functional link between EWS-FLI1 and CD99, two critical biomarkers and therapeutic targets in Ewing sarcoma.
机译：尤文氏肉瘤是一种儿科骨肿瘤，其特征是85％的病例通过 EWS和 FLI1基因之间的融合导致EWS-FLI1异常转录因子的表达。组织学上，尤因肿瘤表达高水平的CD99膜糖蛋白。最近已经描述了CD99表达通过调节肿瘤细胞的生长和分化而有助于尤因肿瘤的发生。不同的研究还表明，EWS-FLI1的过表达在非尤因细胞中诱导CD99表达。相反，通过siRNA方法抑制EWS-FLI1表达对尤因细胞中CD99 mRNA水平没有显着影响。在这里，通过体内和体外研究，我们显示，虽然EWS-FLI1抑制作用对CD99转录物的量仅产生轻微影响，但它诱导CD99蛋白表达水平急剧下降，因此提示-转录调控，可能由microRNA介导。为了进一步研究这个问题，我们鉴定了91个展示EWS-FLI1调节的miRNA，其中三个有望结合CD99 3'非翻译区（3'TR）。其中，我们表明miR-30a-5p具有与CD99的3'-TR区相互作用并调节其表达的能力。此外，在尤因细胞系中miRNA-30a-5p的重新表达诱导了细胞增殖和侵袭的减少。因此，在这项研究中，我们显示miR-30a-5p构成EWS-FLI1和CD99，两个关键生物标记物和尤因肉瘤的治疗靶标之间的主要功能联系。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号