The miR 302-367 cluster drastically affects self-renewal and infiltration properties of glioma-initiating cells through CXCR4 repression and consequent disruption of the SHH-GLI-NANOG network
The miR 302-367 cluster drastically affects self-renewal and infiltration properties of glioma-initiating cells through CXCR4 repression and consequent disruption of the SHH-GLI-NANOG network
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DOI：
10.1038/cdd.2011.89
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发表时间：
2012-02-01
影响因子：
12.4
通讯作者：
Virolle, T.
中科院分区：
文献类型：
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作者：
Fareh, M.;Turchi, L.;Virolle, T.
多形性胶质母细胞瘤（GBM）是成人中最常见的原发性脑肿瘤，通常以生存率低为特征。胶质瘤起始细胞（GiCs）由其广泛的自我更新、分化和肿瘤起始特性定义。已知GiCs参与肿瘤生长和复发，并对常规治疗产生抗性。一种有效靶向GBM中GiC的策略在于抑制它们的干性并因此抑制它们的致瘤特性。在这项研究中，我们发现miR-302-367簇在血清介导的干性抑制过程中被强烈诱导。稳定的miR-302-367簇表达足以通过抑制CXCR 4途径来抑制宿主脑组织内的干性特征、自我更新和细胞浸润。此外，CXCR 4的抑制导致音刺猬（SHH）-GLI-NANOG网络的破坏，该网络参与胚胎干细胞样特征的自我更新和表达。总之，我们证明了miR-302-367簇能够有效地触发级联抑制事件，导致GIC干细胞样和致瘤特性的破坏。Cell Death and Differentiation（2012）19，232-244; doi：10.1038/cdd.2011.89; 2011年7月1日在线发表
Glioblastoma multiforme (GBM) is the most common form of primary brain tumor in adults, often characterized by poor survival. Glioma-initiating cells (GiCs) are defined by their extensive self-renewal, differentiation, and tumor initiation properties. GiCs are known to be involved in tumor growth and recurrence, and in resistance to conventional treatments. One strategy to efficiently target GiCs in GBM consists in suppressing their stemness and consequently their tumorigenic properties. In this study, we show that the miR-302-367 cluster is strongly induced during serum-mediated stemness suppression. Stable miR-302-367 cluster expression is sufficient to suppress the stemness signature, self-renewal, and cell infiltration within a host brain tissue, through inhibition of the CXCR4 pathway. Furthermore, inhibition of CXCR4 leads to the disruption of the sonic hedgehog (SHH)-GLI-NANOG network, which is involved in self-renewal and expression of the embryonic stem cell-like signature. In conclusion, we demonstrated that the miR-302-367 cluster is able to efficiently trigger a cascade of inhibitory events leading to the disruption of GiCs stem-like and tumorigenic properties. Cell Death and Differentiation (2012) 19, 232-244; doi:10.1038/cdd.2011.89; published online 1 July 2011