Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation

被引:910
作者
Mayr, Christine
Hemann, Michael T.
Bartel, David P.
机构
[1] MIT, Howard Hughes Med Inst, Cambridge, MA 02142 USA
[2] MIT, Dept Biol, Cambridge, MA 02142 USA
[3] MIT, Ctr Canc Res, Cambridge, MA 02139 USA
关键词
D O I
10.1126/science.1137999
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
MicroRNAs ( miRNAs) are similar to 22-nucleotide RNAs that can pair to sites within messenger RNAs to specify posttranscriptional repression of these messages. Aberrant miRNA expression can contribute to tumorigenesis, but which of the many miRNA-target relationships are relevant to this process has been unclear. Here, we report that chromosomal translocations previously associated with human tumors disrupt repression of High Mobility Group A2 (Hmga2) by let-7 miRNA. This disrupted repression promotes anchorage-independent growth, a characteristic of oncogenic transformation. Thus, losing miRNA-directed repression of an oncogene provides a mechanism for tumorigenesis, and disrupting a single miRNA-target interaction can produce an observable phenotype in mammalian cells.
引用
收藏
页码:1576 / 1579
页数:4
相关论文
共 27 条
[11]   Sequence-specific inhibition of small RNA function [J].
Hutvágner, G ;
Simard, MJ ;
Mello, CC ;
Zamore, PD .
PLOS BIOLOGY, 2004, 2 (04) :465-475
[12]   Molecular basis of clonal expansion of hematopoiesis in 2 patients with paroxysmal nocturnal hemoglobinuria (PNH) [J].
Inoue, Norimitsu ;
Izui-Sarumaru, Tomohisa ;
Murakami, Yoshiko ;
Endo, Yuichi ;
Nishimura, Jun-Ichi ;
Kurokawa, Ken ;
Kuwayama, Maki ;
Shime, Hiroaki ;
Machii, Takashi ;
Kanakura, Yuzuru ;
Meyers, Gabrielle ;
Wittwer, Carl ;
Chen, Zhong ;
Babcock, William ;
Frei-Lahr, Debra ;
Parker, Charles J. ;
Kinoshita, Taroh .
BLOOD, 2006, 108 (13) :4232-4236
[13]  
Johnson SM, 2005, CELL, V120, P635, DOI 10.1016/j.cell.2005.01.014
[14]   MicroRNAs and their regulatory roles in plants [J].
Jones-Rhoades, Matthew W. ;
Bartel, David P. ;
Bartel, Bonnie .
ANNUAL REVIEW OF PLANT BIOLOGY, 2006, 57 :19-53
[15]   Combinatorial microRNA target predictions [J].
Krek, A ;
Grun, D ;
Poy, MN ;
Wolf, R ;
Rosenberg, L ;
Epstein, EJ ;
MacMenamin, P ;
da Piedade, I ;
Gunsalus, KC ;
Stoffel, M ;
Rajewsky, N .
NATURE GENETICS, 2005, 37 (05) :495-500
[16]   Silencing of microRNAs in vivo with 'antagomirs' [J].
Krützfeldt, J ;
Rajewsky, N ;
Braich, R ;
Rajeev, KG ;
Tuschl, T ;
Manoharan, M ;
Stoffel, M .
NATURE, 2005, 438 (7068) :685-689
[17]   Pervasive regulation of Drosophila Notch target genes by GY-box-, Brd-box-, and K-box-class microRNAs [J].
Lai, EC ;
Tam, B ;
Rubin, GM .
GENES & DEVELOPMENT, 2005, 19 (09) :1067-1080
[18]   Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets [J].
Lewis, BP ;
Burge, CB ;
Bartel, DP .
CELL, 2005, 120 (01) :15-20
[19]   Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs [J].
Lim, LP ;
Lau, NC ;
Garrett-Engele, P ;
Grimson, A ;
Schelter, JM ;
Castle, J ;
Bartel, DP ;
Linsley, PS ;
Johnson, JM .
NATURE, 2005, 433 (7027) :769-773
[20]   Fusion of a sequence from HEI10 (14q11) to the HMGIC gene at 12q15 in a uterine leiomyoma [J].
Mine, N ;
Kurose, K ;
Konishi, H ;
Araki, T ;
Nagai, H ;
Emi, M .
JAPANESE JOURNAL OF CANCER RESEARCH, 2001, 92 (02) :135-139