MicroRNA-21 down-regulates the expression of tumor suppressor PDCD4 in human glioblastoma cell T98G

被引:211
作者
Chen, Yang [1 ,2 ,3 ,4 ]
Liu, Wei [3 ]
Chao, Tengfei [3 ,4 ]
Zhang, Yu [3 ,4 ]
Yan, Xingqi [3 ,4 ]
Gong, Yanhua [3 ]
Qiang, Boqin [3 ]
Yuan, Jiangang [3 ]
Sun, Maosheng [1 ,2 ]
Peng, Xiaozhong [3 ]
机构
[1] Chinese Acad Med Sci, Inst Med Biol, Dept Biochem & Mol Biol, Kunming 650118, Peoples R China
[2] Peking Union Med Coll, Kunming 650118, Peoples R China
[3] Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100005, Peoples R China
[4] Tsinghua Univ, Peking Union Med Coll, Grad Sch, Beijing 100005, Peoples R China
基金
中国国家自然科学基金;
关键词
Glioblastomas; miR-21; PDCD4; T98G;
D O I
10.1016/j.canlet.2008.06.034
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MicroRNAs have been linked to different cancer-related processes. The microRNA miR-21 appears to function as an anti-apoptosis factor in glioblastomas. However, the functional target genes of miR-21 are largely unknown in glioblastomas. In this study, bioinformatics analysis was used to identify miR-21 target sites in various genes. Luciferase activity assay showed that a number of genes involved in apoptosis, PDCD4, MTAP, and SOX5, carry putative miR-21 binding sites. Expression of PDCD4 protein correlates inversely with expression of miR-21 in a number of human glioblastoma cell lines such as T98G, A172, U87, and U251. Inhibition of miR-21 increases endogenous levels of PDCD4 in cell line T98G and over-expression miR-21 inhibits PDCD4-dependent apoptosis. Together, these results indicate that miR-21 expression plays a key role in regulating cellular processes in glioblastomas and may serve as a target for effective therapies. (c) 2008 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:197 / 205
页数:9
相关论文
共 25 条
[1]   MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer [J].
Asangani, I. A. ;
Rasheed, S. A. K. ;
Nikolova, D. A. ;
Leupold, J. H. ;
Colburn, N. H. ;
Post, S. ;
Allgayer, H. .
ONCOGENE, 2008, 27 (15) :2128-2136
[2]   MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells [J].
Chan, JA ;
Krichevsky, AM ;
Kosik, KS .
CANCER RESEARCH, 2005, 65 (14) :6029-6033
[3]   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
[4]   Analysis of the molecular cascade responsible for mesodermal limb chondrogenesis:: Sox genes and BMP signaling [J].
Chimal-Monroy, J ;
Rodriguez-Leon, J ;
Montero, JA ;
Gañan, Y ;
Macias, D ;
Merino, R ;
Hurle, JM .
DEVELOPMENTAL BIOLOGY, 2003, 257 (02) :292-301
[5]   OncomiRs: the discovery and progress of microRNAs in cancers [J].
Cho, William C. S. .
MOLECULAR CANCER, 2007, 6 (1)
[6]   MicroRNA-21 knockdown disrupts glioma growth In vivo and displays synergistic cytotoxicity with neural precursor cell-delivered S-TRAIL in human gliomas [J].
Corsten, Maarten F. ;
Miranda, Rafael ;
Kasmieh, Randa ;
Krichevsky, Anna M. ;
Weissleder, Ralph ;
Shah, Khalid .
CANCER RESEARCH, 2007, 67 (19) :8994-9000
[7]   S6K1- and βTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth [J].
Dorrello, N. Valerio ;
Peschiaroli, Angelo ;
Guardavaccaro, Daniele ;
Colburn, Nancy H. ;
Sherman, Nicholas E. ;
Pagano, Michele .
SCIENCE, 2006, 314 (5798) :467-471
[8]   Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells [J].
Frankel, Lisa B. ;
Christoffersen, Nanna R. ;
Jacobsen, Anders ;
Lindow, Morten ;
Krogh, Anders ;
Lund, Anders H. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (02) :1026-1033
[9]   miR-21 gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism [J].
Fujita, Shuji ;
Ito, Taiji ;
Mizutani, Taketoshi ;
Minoguchi, Shigeru ;
Yamamichi, Nlobutake ;
Sakurai, Kouhei ;
Iba, Hlideo .
JOURNAL OF MOLECULAR BIOLOGY, 2008, 378 (03) :492-504
[10]  
Gao F, 2007, ONCOL REP, V17, P123