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

被引：144

作者：

Fareh, M. ^{[1
]}

Turchi, L. ^{[1
]}

Virolle, V. ^{[1
]}

Debruyne, D. ^{[1
]}

Almairac, F. ^{[1
,2
]}

Divonne, S. de-la-Forest ^{[1
]}

Paquis, P. ^{[2
]}

Preynat-Seauve, O. ^{[3
,4
]}

Krause, K-H ^{[3
,4
]}

Chneiweiss, H. ^{[5
]}

Virolle, T. ^{[1
]}

机构：

[1] Fac Med, INSERM UNSA U898, F-06107 Nice, France

[2] CHU Nice, Hop Pasteur, Serv Neurchirurg, Nice, France

[3] Univ Geneva, Fac Med, Dept Pathol & Immunol, Geneva, Switzerland

[4] Geneva Hosp, Dept Genet & Lab Med, Geneva, Switzerland

[5] Unversite Paris Descartes, INSERM, Ctr Psychiat & Neurosci, U894, Paris, France

来源：

CELL DEATH AND DIFFERENTIATION | 2012年 / 19卷 / 02期

关键词：

miRNA; self-renewal; cancer stem cells; cxcr4; infiltration; CANCER STEM-CELLS; PROTEIN-KINASE; PROLIFERATION; GLIOBLASTOMA; TUMORS;

D O I：

10.1038/cdd.2011.89

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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

引用

页码：232 / 244

页数：13

共 38 条

[1] Dynamic distribution and stem cell characteristics of Sox1-expressing cells in the cerebellar cortex [J].