Suppression of cell growth and invasion by miR-205 in breast cancer

被引:283
作者
Wu, Hailong [1 ]
Zhu, Shoumin [1 ]
Mo, Yin-Yuan [1 ]
机构
[1] So Illinois Univ, Sch Med, Dept Med Microbiol Immunol & Cell Biol, Springfield, IL 62794 USA
关键词
breast cancer; cell growth; ErbB3; miRNA; miR-205; post-transcriptional regulation; VEGF-A; ANCHORAGE-INDEPENDENT GROWTH; HUMAN MICRORNA GENES; DOWN-REGULATION; EXPRESSION; TARGETS; ERBB3; SEED; METASTASIS; RNAS; TRANSCRIPTS;
D O I
10.1038/cr.2009.18
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
MicroRNAs (miRNAs) are endogenous, small, non-coding RNAs, which are capable of silencing gene expression at the post-transcriptional level. In this study, we report that miR-205 is significantly underexpressed in breast tumor compared to the matched normal breast tissue. Similarly, breast cancer cell lines, including MCF-7 and MDA-MB231, express a lower level miR-205 than the non-malignant MCF-10A cells. Of interest, ectopic expression of miR-205 significantly inhibits cell proliferation and anchorage independent growth, as well as cell invasion. Furthermore, miR-205 was shown to suppress lung metastasis in an animal model. Finally, western blot combined with the luciferase reporter assays demonstrate that ErbB3 and vascular endothelial growth factor A (VEGF-A) are direct targets for miR-205, and this miR-205-mediated suppression is likely through the direct interaction with the putative miR-205 binding site in the 3'-untranslated region (3'-UTR) of ErbB3 and VEGF-A. Together, these results suggest that miR-205 is a tumor suppressor in breast cancer.
引用
收藏
页码:439 / 448
页数:10
相关论文
共 58 条
[1]   Differences in vertebrate microRNA expression [J].
Ason, Brandon ;
Darnell, Diana K. ;
Wittbrodt, Beate ;
Berezikov, Eugene ;
Kloosterman, Wigard P. ;
Wittbrodt, Jochen ;
Antin, Parker B. ;
Plasterk, Ronald H. A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (39) :14385-14389
[2]  
Bachelder RE, 2002, CANCER RES, V62, P7203
[3]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[4]   Phylogenetic shadowing and computational identification of human microRNA genes [J].
Berezikov, E ;
Guryev, V ;
van de Belt, J ;
Wienholds, E ;
Plasterk, RHA ;
Cuppen, E .
CELL, 2005, 120 (01) :21-24
[5]   Trans-splicing and polyadenylation of let-7 microRNA primary transcripts [J].
Bracht, J ;
Hunter, S ;
Eachus, R ;
Weeks, P ;
Pasquinelli, AE .
RNA, 2004, 10 (10) :1586-1594
[6]   Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs [J].
Cai, XZ ;
Hagedorn, CH ;
Cullen, BR .
RNA, 2004, 10 (12) :1957-1966
[7]   Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia [J].
Calin, GA ;
Dumitru, CD ;
Shimizu, M ;
Bichi, R ;
Zupo, S ;
Noch, E ;
Aldler, H ;
Rattan, S ;
Keating, M ;
Rai, K ;
Rassenti, L ;
Kipps, T ;
Negrini, M ;
Bullrich, F ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (24) :15524-15529
[8]   Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers [J].
Calin, GA ;
Sevignani, C ;
Dan Dumitru, C ;
Hyslop, T ;
Noch, E ;
Yendamuri, S ;
Shimizu, M ;
Rattan, S ;
Bullrich, F ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (09) :2999-3004
[9]   MicroRNA signatures in human cancers [J].
Calin, George A. ;
Croce, Carlo M. .
NATURE REVIEWS CANCER, 2006, 6 (11) :857-866
[10]   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