微小RNA-34a通过靶向Notch信号通路诱导胶质瘤干细胞向血管内皮细胞转分化。
MicroRNA-34a induces transdifferentiation of glioma stem cells into vascular endothelial cells by targeting Notch pathway.
作者信息
Jin Zaishun, Zhan Tao, Tao Jing, Xu Biao, Zheng Huizhe, Cheng Yongxia, Yan Bin, Wang Hongwei, Lu Guoqiang, Lin Ying, Guo Sufen
机构信息
a Key Laboratory of Cancer Prevention and Treatment of Heilongjiang Province , Mudanjiang Medical University , Mudanjiang , People's Republic of China.
b Department of Pathology , Mudanjiang Medical University , Mudanjiang , People's Republic of China.
出版信息
Biosci Biotechnol Biochem. 2017 Oct;81(10):1899-1907. doi: 10.1080/09168451.2017.1364965. Epub 2017 Sep 1.
The function of microRNA-34a (miR-34a) in transdifferentiation of glioma stem cells (GSCs) into vascular endothelial cells (VECs) was explored by focusing on Notch ligand Delta-like 1 (Dll1). MiR-34a mimics was transfected into CD133 + glioma cell U251. The angiogenesis feature of miR-34a transfected U251 cells was investigated and the expressions of CD31, CD34, Vwf, Notch 1, and Dll1 were quantified. Length of branching vessel-like structures in the miR-34a transfected U251 cells was significantly higher than control cells. The VEC feature of miR-34a overexpressed U251 cells was further confirmed by the expressions of CD31, CD34, and vWF. Transfection of miR-34a decreased the expression of Notch 1 and Dll1. Furthermore, the miR-34a overexpression-enhanced tube formation of GSCs was suppressed when the decreased expression of Dll1 was restored. The current study highlighted the potential of miR-34a as an inducer in GSCs' transdifferentiation into VECs by targeting Dll1.
通过聚焦Notch配体Delta样1（Dll1），探讨了微小RNA-34a（miR-34a）在胶质瘤干细胞（GSCs）向血管内皮细胞（VECs）转分化中的作用。将miR-34a模拟物转染到CD133 +胶质瘤细胞U251中。研究了转染miR-34a的U251细胞的血管生成特征，并对CD31、CD34、血管性血友病因子（Vwf）、Notch 1和Dll1的表达进行了定量分析。转染miR-34a的U251细胞中分支状血管样结构的长度显著高于对照细胞。CD31、CD34和vWF的表达进一步证实了过表达miR-34a的U251细胞具有VEC特征。miR-34a转染降低了Notch 1和Dll1的表达。此外，当Dll1表达降低得到恢复时，miR-34a过表达增强的GSCs管腔形成受到抑制。当前研究突出了miR-34a通过靶向Dll1作为GSCs向VECs转分化诱导剂的潜力。
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