打开APP

JCI:促发儿童骨肿瘤的非编码RNA

  1. 尤文氏肉瘤
  2. 非编码RNA

来源:生物谷 2014-11-19 13:35

非编码RNA促进小儿骨肿瘤尤文氏肉瘤是骨或其周围软组织癌症,主要影响儿童和年轻成人。尤文氏肉瘤的特点是易位事件,导致RNA结合蛋白被称为EWS与转录因子,如FLI1的融合。以前的工作表明,该融合蛋白EWS-FLI1促进癌

2014年11月19日讯 /生物谷BIOON/ --尤文氏肉瘤是骨或其周围软组织癌症,主要影响儿童和年轻成人。尤文氏肉瘤的特点是易位事件的发生,即RNA结合蛋白——EWS与转录因子如FLI1的融合。

以前的研究工作表明,该融合蛋白EWS-FLI1通过改变基因表达,促进癌症,但融合蛋白作用的靶基因是未知的。

发表在Journal of Clinical Investigation杂志上的最新研究表明,一种长链非编码RNA即尤因肉瘤相关转录物1(EWSAT1)是融合蛋白的一个重要作用靶标。

斯坦福大学Alejandro Sweet-Cordero为首的科研团队,确定了尤文氏肉瘤儿童癌细胞EWSAT1的表达增加。此外,他们发现,这种非编码RNA对于癌细胞的生长是重要的,并与EWS-FLI1下游的几种基因相关联。

研究工作证实长链非编码RNA可以是尤因肉瘤的关键驱动因子。(生物谷Bioon.com)

本文系生物谷原创编译整理,欢迎转载!转载请注明来源并附原文链接。谢谢!

Long noncoding RNA EWSAT1-mediated gene repression facilitates Ewing sarcoma oncogenesis

Michelle Marques Howarth,et al.

Chromosomal translocation that results in fusion of the genes encoding RNA-binding protein EWS and transcription factor FLI1 (EWS-FLI1) is pathognomonic for Ewing sarcoma. EWS-FLI1 alters gene expression through mechanisms that are not completely understood. We performed RNA sequencing (RNAseq) analysis on primary pediatric human mesenchymal progenitor cells (pMPCs) expressing EWS-FLI1 in order to identify gene targets of this oncoprotein. We determined that long noncoding RNA-277 (Ewing sarcoma–associated transcript 1 [EWSAT1]) is upregulated by EWS-FLI1 in pMPCs. Inhibition of EWSAT1 expression diminished the ability of Ewing sarcoma cell lines to proliferate and form colonies in soft agar, whereas EWSAT1 inhibition had no effect on other cell types tested. Expression of EWS-FLI1 and EWSAT1 repressed gene expression, and a substantial fraction of targets that were repressed by EWS-FLI1 were also repressed by EWSAT1. Analysis of RNAseq data from primary human Ewing sarcoma further supported a role for EWSAT1 in mediating gene repression. We identified heterogeneous nuclear ribonucleoprotein (HNRNPK) as an RNA-binding protein that interacts with EWSAT1 and found a marked overlap in HNRNPK-repressed genes and those repressed by EWS-FLI1 and EWSAT1, suggesting that HNRNPK participates in EWSAT1-mediated gene repression. Together, our data reveal that EWSAT1 is a downstream target of EWS-FLI1 that facilitates the development of Ewing sarcoma via the repression of target genes.

 

版权声明 本网站所有注明“来源:生物谷”或“来源:bioon”的文字、图片和音视频资料,版权均属于生物谷网站所有。非经授权,任何媒体、网站或个人不得转载,否则将追究法律责任。取得书面授权转载时,须注明“来源:生物谷”。其它来源的文章系转载文章,本网所有转载文章系出于传递更多信息之目的,转载内容不代表本站立场。不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。

87%用户都在用生物谷APP 随时阅读、评论、分享交流 请扫描二维码下载->