Functional Differences of miR-125b on the Invasion of Primary Glioblastoma CD133-Negative Cells and CD133-Positive Cells

被引:38
作者
Shi, Lei [1 ]
Wan, Yi [2 ]
Sun, Guan [3 ]
Gu, Xiaoyan [4 ]
Qian, Chunfa [5 ]
Yan, Wei [6 ]
Zhang, Shuguang [1 ]
Pan, Tianhong [1 ]
Wang, Zhimin [2 ]
You, Yongping [6 ]
机构
[1] Jiangsu Univ, Dept Neurosurg, Peoples Hosp Kunshan 1, Suzhou 215300, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Dept Neurosurg, Suzhou Kowloon Hosp, Suzhou 215021, Peoples R China
[3] Nantong Univ, Dept Neurosurg, Affiliated Yancheng Hosp 4, Yancheng 224000, Peoples R China
[4] Chinese PLA, Dept Resp Med, Hosp 454, Nanjing 210002, Jiangsu, Peoples R China
[5] Nanjing Med Univ, Dept Neurosurg, Affiliated Brain Hosp, Nanjing 210029, Jiangsu, Peoples R China
[6] Nanjing Med Univ, Dept Neurosurg, Affiliated Hosp 1, Nanjing 210029, Jiangsu, Peoples R China
关键词
MicroRNA; Glioblastoma; Stem cells; HUMAN GLIOMA-CELLS; TUMOR STEM-CELLS; HUMAN BRAIN; EXPRESSION; DIFFERENTIATION; PROLIFERATION; CANCER; TEMOZOLOMIDE; MICRORNA-21; APOPTOSIS;
D O I
10.1007/s12017-012-8188-8
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
MicroRNAs (miRNAs) are small noncoding RNAs whose function as modulators of gene expression is crucial for the proper control of cell development, differentiation, and homeostasis. The total number and composition of miRNAs expressed per cell at different stages of development varies widely, and the same miRNA may function differently at different stages of development. In this prospective study, we evaluated the function of miR-125b at different developmental stages of glioblastoma cells, such as primary glioblastoma cells and the corresponding stem cells. CD133 is an important surface marker in glioblastoma stem cells. We found that the upregulation of miR-125b had no effects on the invasion of primary glioblastoma CD133-negative cells but that it could inhibit the invasion of corresponding CD133-positive cells; however, the downregulation of miR-125b also had no effects on the invasion of primary glioblastoma CD133-negative cells but promoted the invasion of CD133-positive cells. Further research into the underlying mechanism demonstrated that the effects of miR-125b on the invasion of glioblastoma CD133-positive cells were associated with the alteration of the expression of MMPs (MMP-2 and MMP-9) and corresponding inhibitors (RECK and TIMP3). Our results demonstrate that miR-125b expression plays an essential role in the invasion of glioblastoma CD133-positive cells but not CD133-negative cells. Therefore, miR-125b may represent a novel target for therapy targeting the invasion of glioblastoma stem cells in the future.
引用
收藏
页码:303 / 316
页数:14
相关论文
共 34 条
[1]   Cannabinoids inhibit glioma cell invasion by down-regulating matrix metalloproteinase-2 expression [J].
Blazquez, Cristina ;
Salazar, Maria ;
Carracedo, Arkaitz ;
Lorente, Mar ;
Egia, Ainara ;
Gonzalez-Feria, Luis ;
Haro, Amador ;
Velasco, Guillermo ;
Guzman, Manuel .
CANCER RESEARCH, 2008, 68 (06) :1945-1952
[2]   Stem cell-like micro-RNA signature driven by Myc in aggressive liver cancer [J].
Cairo, Stefano ;
Wang, Yipeng ;
de Reynies, Aurelien ;
Duroure, Karine ;
Dahan, Jennifer ;
Redon, Marie-Jose ;
Fabre, Monique ;
McClelland, Michael ;
Wang, Xin W. ;
Croce, Carlo M. ;
Buendia, Marie-Annick .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (47) :20471-20476
[3]  
Cao Yiting, 2010, Genes Cancer, V1, P50
[4]   MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells [J].
Chan, JA ;
Krichevsky, AM ;
Kosik, KS .
CANCER RESEARCH, 2005, 65 (14) :6029-6033
[5]   Real-time quantification of microRNAs by stem-loop RT-PCR [J].
Chen, CF ;
Ridzon, DA ;
Broomer, AJ ;
Zhou, ZH ;
Lee, DH ;
Nguyen, JT ;
Barbisin, M ;
Xu, NL ;
Mahuvakar, VR ;
Andersen, MR ;
Lao, KQ ;
Livak, KJ ;
Guegler, KJ .
NUCLEIC ACIDS RESEARCH, 2005, 33 (20) :e179.1-e179.9
[6]   Elevated invasive potential of glioblastoma stem cells [J].
Cheng, Lin ;
Wu, Qiulian ;
Guryanova, Olga A. ;
Huang, Zhi ;
Huang, Qian ;
Rich, Jeremy N. ;
Bao, Shideng .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2011, 406 (04) :643-648
[7]   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
[8]  
Darling JL, 1990, NEUROONCOLOGY PRIMAR, P1
[9]   MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators [J].
Gabriely, Galina ;
Wurdinger, Thomas ;
Kesari, Santosh ;
Esau, Christine C. ;
Burchard, Julja ;
Linsley, Peter S. ;
Krichevsky, Anna M. .
MOLECULAR AND CELLULAR BIOLOGY, 2008, 28 (17) :5369-5380
[10]   Stem cell division is regulated by the microRNA pathway [J].
Hatfield, SD ;
Shcherbata, HR ;
Fischer, KA ;
Nakahara, K ;
Carthew, RW ;
Ruohola-Baker, H .
NATURE, 2005, 435 (7044) :974-978