MicroRNA-153 is tumor suppressive in glioblastoma stem cells

被引:59
作者
Zhao, Shiguang [1 ,2 ]
Deng, Yifan [1 ,2 ]
Liu, Yaohua [1 ,2 ]
Chen, Xin [1 ,2 ]
Yang, Guang [1 ,2 ]
Mu, Yulong [1 ,2 ]
Zhang, Daming [1 ,2 ]
Kang, Jianhao [1 ,2 ]
Wu, Zhaoli [1 ,2 ]
机构
[1] Harbin Med Univ, Affiliated Hosp 1, Dept Neurosurg, Harbin 150001, Heilongjiang, Peoples R China
[2] Harbin Med Univ, Inst Brain Sci, Harbin 150001, Heilongjiang, Peoples R China
关键词
Glioblastoma multiforme; Glioblastoma stem cells; MiR-153; Self-renewal ability; Differentiation; SELF-RENEWAL; GLIOMA; EXPRESSION; PATHWAY; TARGETS;
D O I
10.1007/s11033-012-2278-4
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 lethal brain tumor thought to arise from GBM stem cells (GBM-SCs). MicroRNAs carry out post-transcriptional regulation of various cellular processes that modulate the stemness properties of GBM-SCs. Here, we investigated the critical role of miR-153 in GBM-SCs. First, GBM-SCs were isolated from six GBM specimens. These GBM-SCs formed GBM spheres, expressed markers associated with neural stem cells, and possessed the capacity for self-renewal and multilineage differentiation. Then qRT-PCR analysis showed that miR-153 expression was down-regulated in GBM tissues relative to normal brain tissues, and in CD133 positive cells relative to CD133 negative cells. This project demonstrates for the first time that transient transfection of miR-153 into GBM-SCs can inhibit their stemness properties, such as impairing self-renewal ability and inducing differentiation. Meanwhile, miR-153 can also repress GBM-SCs growth and induce apoptosis. Altogether, these results indicate that reactivation of miR-153 expression suggests novel therapeutic strategies for GBM-SCs.
引用
收藏
页码:2789 / 2798
页数:10
相关论文
共 34 条
[11]   Characterization of microRNA expression levels and their biological correlates in human cancer cell lines [J].
Gaur, Arti ;
Jewell, David A. ;
Liang, Yu ;
Ridzon, Dana ;
Moore, Jason H. ;
Chen, Caifu ;
Ambros, Victor R. ;
Israel, Mark A. .
CANCER RESEARCH, 2007, 67 (06) :2456-2468
[12]   MicroRNAs and glioblastoma; the stem cell connection [J].
Godlewski, J. ;
Newton, H. B. ;
Chiocca, E. A. ;
Lawler, S. E. .
CELL DEATH AND DIFFERENTIATION, 2010, 17 (02) :221-228
[13]   The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo [J].
Huse, Jason T. ;
Brennan, Cameron ;
Hambardzumyan, Dolores ;
Wee, Boyoung ;
Pena, John ;
Rouhanifard, Sara H. ;
Sohn-Lee, Cherin ;
le Sage, Carlos ;
Agami, Reuven ;
Tuschl, Thomas ;
Holland, Eric C. .
GENES & DEVELOPMENT, 2009, 23 (11) :1327-1337
[14]   Wnt-mediated self-renewal of neural stem/progenitor cells [J].
Kalani, M. Yashar S. ;
Cheshier, Samuel H. ;
Cord, Branden J. ;
Bababeygy, Simon R. ;
Vogel, Hannes ;
Weissman, Irving L. ;
Palmer, Theo D. ;
Nusse, Roel .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (44) :16970-16975
[15]   MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy [J].
Kasinski, Andrea L. ;
Slack, Frank J. .
NATURE REVIEWS CANCER, 2011, 11 (12) :849-864
[16]   MicroRNA-34a Inhibits Glioblastoma Growth by Targeting Multiple Oncogenes [J].
Li, Yunqing ;
Guessous, Fadila ;
Zhang, Ying ;
DiPierro, Charles ;
Kefas, Benjamin ;
Johnson, Elizabeth ;
Marcinkiewicz, Lukasz ;
Jiang, Jinmai ;
Yang, Yanzhi ;
Schmittgen, Thomas D. ;
Lopes, Beatriz ;
Schiff, David ;
Purow, Benjamin ;
Abounader, Roger .
CANCER RESEARCH, 2009, 69 (19) :7569-7576
[17]   MicroRNA-153 negatively regulates the expression of amyloid precursor protein and amyloid precursor-like protein 2 [J].
Liang, Chunlian ;
Zhu, Hua ;
Xu, Yanfeng ;
Huang, Lan ;
Ma, Chunmei ;
Deng, Wei ;
Liu, Ying ;
Qin, Chuan .
BRAIN RESEARCH, 2012, 1455 :103-113
[18]   MicroRNA expression profiles classify human cancers [J].
Lu, J ;
Getz, G ;
Miska, EA ;
Alvarez-Saavedra, E ;
Lamb, J ;
Peck, D ;
Sweet-Cordero, A ;
Ebet, BL ;
Mak, RH ;
Ferrando, AA ;
Downing, JR ;
Jacks, T ;
Horvitz, HR ;
Golub, TR .
NATURE, 2005, 435 (7043) :834-838
[19]   MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells [J].
Papagiannakopoulos, Thales ;
Shapiro, Alice ;
Kosik, Kenneth S. .
CANCER RESEARCH, 2008, 68 (19) :8164-8172
[20]   Glioma Stem Cell Lines Expanded in Adherent Culture Have Tumor-Specific Phenotypes and Are Suitable for Chemical and Genetic Screens [J].
Pollard, Steven M. ;
Yoshikawa, Koichi ;
Clarke, Ian D. ;
Danovi, Davide ;
Stricker, Stefan ;
Russell, Roslin ;
Bayani, Jane ;
Head, Renee ;
Lee, Marco ;
Bernstein, Mark ;
Squire, Jeremy A. ;
Smith, Austin ;
Dirks, Peter .
CELL STEM CELL, 2009, 4 (06) :568-580