Musashi1 (Msi1) is a highly conserved RNA-binding protein that is required during the development of the nervous system. Msi1 has been characterized as a stem cell marker, controlling the balance between self-renewal and differentiation, and has also been implicated in tumorigenesis, being highly expressed in multiple tumor types. We analyzed Msi1 expression in a large cohort of medulloblastoma samples and found that Msi1 is highly expressed in tumor tissue compared with normal cerebellum. Notably, high Msi1 expression levels proved to be a sign of poor prognosis. Msi1 expression was determined to be particularly high in molecular subgroups 3 and 4 of medulloblastoma. We determined that Msi1 is required for tumorigenesis because inhibition of Msi1 expression by small-interfering RNAs reduced the growth of Daoy medulloblastoma cells in xenografts. To characterize the participation of Msi1 in medulloblastoma, we conducted different high-throughput analyses. Ribonucleoprotein immunoprecipitation followed by microarray analysis (RIP-chip) was used to identify mRNA species preferentially associated with Msi1 protein in Daoy cells. We also used cluster analysis to identify genes with similar or opposite expression patterns to Msi1 in our medulloblastoma cohort. A network study identified RAC1, CTGF, SDCBP, SRC, PRL, and SHC1 as major nodes of an Msi1-associated network. Our results suggest that Msi1 functions as a regulator of multiple processes in medulloblastoma formation and could become an important therapeutic target.

译文

Musashi1 (Msi1) 是一种高度保守的RNA结合蛋白,在神经系统发育过程中是必需的。Msi1已被表征为干细胞标志物,控制自我更新和分化之间的平衡,并且还与肿瘤发生有关,在多种肿瘤类型中高度表达。我们分析了Msi1在大量髓母细胞瘤样本中的表达,发现与正常小脑相比,Msi1在肿瘤组织中高表达。值得注意的是,高Msi1表达水平被证明是预后不良的迹象。确定Msi1在髓母细胞瘤的分子亚组3和4中表达特别高。我们确定Msi1是肿瘤发生所必需的,因为小干扰rna抑制Msi1表达会降低异种移植物中Daoy髓母细胞瘤细胞的生长。为了表征Msi1参与髓母细胞瘤的情况,我们进行了不同的高通量分析。核糖核蛋白免疫沉淀,然后进行微阵列分析 (RIP-chip),用于鉴定Daoy细胞中优先与Msi1蛋白相关的mRNA种类。我们还使用聚类分析来鉴定在我们的髓母细胞瘤队列中具有与Msi1相似或相反表达模式的基因。一项网络研究将RAC1,CTGF,SDCBP,SRC,PRL和SHC1确定为Msi1-associated网络的主要节点。我们的结果表明,Msi1在髓母细胞瘤形成中充当多个过程的调节剂,并可能成为重要的治疗靶标。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录