Deregulation of microRNA expression in the different genetic subtypes of multiple myeloma and correlation with gene expression profiling

被引：175
作者：
Gutierrez, N. C. [1 ]
Sarasquete, M. E. [1 ]
Misiewicz-Krzeminska, I. [1 ]
Delgado, M. [1 ]
De Las Rivas, J. [2 ]
Ticona, F. V. [1 ]
Ferminan, E. [3 ]
Martin-Jimenez, P. [1 ]
Chillon, C. [1 ]
Risueno, A. [2 ]
Hernandez, J. M. [1 ]
Garcia-Sanz, R. [1 ]
Gonzalez, M. [1 ]
San Miguel, J. F. [1 ]
机构：
[1] Hosp Univ Salamanca, Serv Hematol, Ctr Invest Canc, IBMCC,USAL,CSIC, Salamanca 37007, Spain
[2] CSIC, USAL, Ctr Invest Canc, Grp Bioinformat & Genom Func,IBMCC, Salamanca, Spain
[3] CSIC, USAL, Ctr Invest Canc, Unidad Genom,IBMCC, Salamanca, Spain
来源：
LEUKEMIA | 2010年 / 24卷 / 03期
关键词：
microRNA; myeloma; gene expression; KAPPA-B; LEUKEMIA; IDENTIFICATION; MECHANISMS; SIGNATURES; APOPTOSIS; MIRNAS; CELLS; TRANSFORMATION; PROLIFERATION;
D O I：
10.1038/leu.2009.274
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Specific microRNA (miRNA) signatures have been associated with different cytogenetic subtypes in acute leukemias. This finding prompted us to investigate potential associations between genetic abnormalities in multiple myeloma (MM) and singular miRNA expression profiles. Moreover, global gene expression profiling was also analyzed to find correlated miRNA gene expression and select miRNA target genes that show such correlation. For this purpose, we analyzed the expression level of 365 miRNAs and the gene expression profiling in 60 newly diagnosed MM patients, selected to represent the most relevant recurrent genetic abnormalities. Supervised analysis showed significantly deregulated miRNAs in the different cytogenetic subtypes as compared with normal PC. It is interesting to note that miR-1 and miR-133a clustered on the same chromosomal loci, were specifically over-expressed in the cases with t(14;16). The analysis of the relationship between miRNA expression and their respective target genes showed a conserved inverse correlation between several miRNAs deregulated in MM cells and CCND2 expression level. These results illustrate, for the first time, that miRNA expression pattern in MM is associated with genetic abnormalities, and that the correlation of the expression profile of miRNA and their putative mRNA targets is useful to find statistically significant protein-coding genes in MM pathogenesis associated with changes in specific miRNAs. Leukemia (2010) 24, 629-637; doi:10.1038/leu.2009.274; published online 7 January 2010
引用
收藏
页码：629 / 637
页数：9
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