Pro-neural miR-128 is a glioma tumor suppressor that targets mitogenic kinases

被引：154

作者：

Papagiannakopoulos, T. ^{[1
,2
]}

Friedmann-Morvinski, D. ^{[3
]}

Neveu, P. ^{[2
,4
]}

Dugas, J. C. ^{[5
]}

Gill, R. M. ^{[1
,2
]}

Huillard, E. ^{[6
,7
]}

Liu, C. ^{[8
]}

Zong, H. ^{[8
]}

Rowitch, D. H. ^{[6
,7
,9
,10
]}

Barres, B. A. ^{[5
]}

Verma, I. M. ^{[3
]}

Kosik, K. S. ^{[1
,2
]}

机构：

[1] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA

[2] Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA

[3] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA

[4] Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Santa Barbara, CA 93106 USA

[5] Stanford Univ, Sch Med, Dept Neurobiol, Stanford, CA 94305 USA

[6] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA

[7] Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA USA

[8] Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA

[9] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA USA

[10] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA

来源：

ONCOGENE | 2012年 / 31卷 / 15期

基金：

美国国家科学基金会;

关键词：

microRNA; glioma stem cells; miR-128; EGFR; PDGFR alpha; GROWTH-FACTOR RECEPTOR; STEM-CELL; IN-VIVO; MICRORNAS; BRAIN; EGFR; MODULATION; MECHANISMS; RENEWAL; SET;

D O I：

10.1038/onc.2011.380

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：

MicroRNAs (miRNAs) carry out post-transcriptional control of a multitude of cellular processes. Aberrant expression of miRNA can lead to diseases, including cancer. Gliomas are aggressive brain tumors that are thought to arise from transformed glioma-initiating neural stem cells (giNSCs). With the use of giNSCs and human glioblastoma cells, we investigated the function of miRNAs in gliomas. We identified pro-neuronal miR-128 as a candidate glioma tumor suppressor miRNA. Decreased expression of miR-128 correlates with aggressive human glioma subtypes. With a combination of molecular, cellular and in vivo approaches, we characterize miR-128's tumor suppressive role. miR-128 represses giNSC growth by enhancing neuronal differentiation. miR-128 represses growth and mediates differentiation by targeting oncogenic receptor tyrosine kinases (RTKs) epithelial growth factor receptor and platelet-derived growth factor receptor-alpha. Using an autochthonous glioma mouse model, we demonstrated that miR-128 repressed gliomagenesis. We identified miR-128 as a glioma tumor suppressor that targets RTK signaling to repress giNSC self-renewal and enhance differentiation. Oncogene (2012) 31, 1884-1895; doi:10.1038/onc.2011.380; published online 29 August 2011

引用

页码：1884 / 1895

页数：12

共 38 条

[1] Epidermal growth factor receptor and Ink4a/Arf:: Convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis [J].

Bachoo, RM ;

Maher, EA ;

Ligon, KL ;

Sharpless, NE ;

Chan, SS ;

You, MJJ ;

Tang, Y ;

DeFrances, J ;

Stover, E ;

Weissleder, R ;

Rowitch, DH ;

Louis, DN ;

DePinho, RA .

CANCER CELL, 2002, 1 (03) :269-277

[2] Constitutive EGFR signaling confers a motile phenotype to neural stem cells [J].

Boockvar, JA ;

Kapitonov, D ;

Kapoor, G ;

Schouten, J ;

Counelis, GJ ;

Bogler, O ;

Snyder, EY ;

McIntosh, TK ;

O'Rourke, DM .

MOLECULAR AND CELLULAR NEUROSCIENCE, 2003, 24 (04) :1116-1130

[3] miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche [J].

Cheng, Li-Chun ;

Pastrana, Erika ;

Tavazoie, Masoud ;

Doetsch, Fiona .

NATURE NEUROSCIENCE, 2009, 12 (04) :399-408

[4] Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].

Chin, L. ;

Meyerson, M. ;

Aldape, K. ;

Bigner, D. ;

Mikkelsen, T. ;

VandenBerg, S. ;

Kahn, A. ;

Penny, R. ;

Ferguson, M. L. ;

Gerhard, D. S. ;

Getz, G. ;

Brennan, C. ;

Taylor, B. S. ;

Winckler, W. ;

Park, P. ;

Ladanyi, M. ;

Hoadley, K. A. ;

Verhaak, R. G. W. ;

Hayes, D. N. ;

Spellman, Paul T. ;

Absher, D. ;

Weir, B. A. ;

Ding, L. ;

Wheeler, D. ;

Lawrence, M. S. ;

Cibulskis, K. ;

Mardis, E. ;

Zhang, Jinghui ;

Wilson, R. K. ;

Donehower, L. ;

Wheeler, D. A. ;

Purdom, E. ;

Wallis, J. ;

Laird, P. W. ;

Herman, J. G. ;

Schuebel, K. E. ;

Weisenberger, D. J. ;

Baylin, S. B. ;

Schultz, N. ;

Yao, Jun ;

Wiedemeyer, R. ;

Weinstein, J. ;

Sander, C. ;

Gibbs, R. A. ;

Gray, J. ;

Kucherlapati, R. ;

Lander, E. S. ;

Myers, R. M. ;

Perou, C. M. ;

McLendon, Roger .

NATURE, 2008, 455 (7216) :1061-1068

[5] Extensive modulation of a set of microRNAs in primary glioblastoma [J].

Ciafrè, SA ;

Galardi, S ;

Mangiola, A ;

Ferracin, M ;

Liu, CG ;

Sabatino, G ;

Negrini, M ;

Maira, G ;

Croce, CM ;

Farace, MG .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 334 (04) :1351-1358

[6] Reciprocal actions of REST and a microRNA promote neuronal identity [J].

Conaco, C ;

Otto, S ;

Han, JJ ;

Mandel, G .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (07) :2422-2427

[7] miR-21 and 221 upregulation and miR-181b downregulation in human grade II-IV astrocytic tumors [J].

Conti, Alfredo ;

Aguennouz, M'Hammed ;

La Torre, Domenico ;

Tomasello, Chiara ;

Cardali, Salvatore ;

Angileri, Filippo F. ;

Maio, Francesca ;

Cama, Annamaria ;

Germano, Antonino ;

Vita, Giuseppe ;

Tomasello, Francesco .

JOURNAL OF NEURO-ONCOLOGY, 2009, 93 (03) :325-332

[8] PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo [J].

Dai, C ;

Celestino, JC ;

Okada, Y ;

Louis, DN ;

Fuller, GN ;

Holland, EC .

GENES & DEVELOPMENT, 2001, 15 (15) :1913-1925

[9] EGF converts transit-amplifying neurogenic precursors in the adult brain into multipotent stem cells [J].

Doetsch, F ;

Petreanu, L ;

Caille, I ;

Garcia-Verdugo, JM ;

Alvarez-Buylla, A .

NEURON, 2002, 36 (06) :1021-1034

[10] Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? [J].

Filipowicz, Witold ;

Bhattacharyya, Suvendra N. ;

Sonenberg, Nahum .

NATURE REVIEWS GENETICS, 2008, 9 (02) :102-114

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