Deregulation of microRNA expression in the different genetic subtypes of multiple myeloma and correlation with gene expression profiling.
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 overexpressed 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.
Gutiérrez
N C
NC
Servicio de Hematología, Hospital Universitario, Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca, Spain.
Sarasquete
M E
ME
Misiewicz-Krzeminska
I
I
Delgado
M
M
De Las Rivas
J
J
Ticona
F V
FV
Fermiñán
E
E
Martín-Jiménez
P
P
Chillón
C
C
Risueño
A
A
Hernández
J M
JM
García-Sanz
R
R
González
M
M
San Miguel
J F
JF
D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D051928:CD47 Antigen / Q000235:genetics; D002869:Chromosome Aberrations; D056742:Cyclin D2 / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000032:analysis*; D009101:Multiple Myeloma / Q000209:etiology / Q000235:genetics*
C491123:BACH2 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; C080336:CCND2 protein, human; D051928:CD47 Antigen; C497894:CD47 protein, human; D056742:Cyclin D2; D035683:MicroRNAs