E-GEOD-40308 - Downregulation of specific miRNAs in hyperdiploid multiple myeloma mimics the oncogenic effect of IgH translocations occurring in the non-hyperdiploid subtype
Released on 3 December 2013, last updated on 13 May 2014
Currently, multiple myeloma (MM) patients are broadly grouped into a non-hyperdiploid Group (nh-MM), highly enriched for IgH translocations, or into a hyperdiploid Group (h-MM), which is typically characterized by trisomies of some odd-numbered chromosomes. We compared the miRNA expression profiles of these two groups and we identified 16 miRNAs that were downregulated in the h-MM group, relative to the nh-MM group. We found that target genes of the most differentially expressed miRNAs are directly involved in the pathogenesis of MM; specifically, the inhibition of hsa-miR-425, hsa-miR-152 and hsa-miR-24, which are all downregulated in h-MM, leads to the overexpression of CCND1, TACC3, MAFB, FGFR3 and MYC, which are the also the oncogenes upregulated by the most frequent IgH chromosomal translocations occurring in nh-MM. Importantly, we showed that the downregulation of these specific miRNAs and the upregulation of their targets also occur simultaneously in primary cases of h-MM. These data provide further evidence on the unifying role of cyclin C pathways deregulation as the key mechanism involved in the development of both groups of MM. Finally, they establish the importance of miRNA deregulation in the context of MM, thereby opening up the potential for future therapeutic approaches based on this molecular mechanism. miRNA expression profiling: The discovery series was composed of 53 CD138-positive de novo primary cases of Multiple Myeloma, of which 36 were classified as nh-MM and 17 as h-MM. Also included in this first analysis were 7 MM cell lines, six (JJN3, L363, OPM-2, K620, KMS28BM, KMS28PE) representing the nh-MM subtype and one (OH-2) as the model for h-MM. All samples, primary cases and cell lines, were labeled and hybridized in duplicate to the ‘8-pack’ Human miRNA Oligo Microarray G4470A (Agilent Technologies). We differentially expressed miRNA expression between the nh-MM and the h-MM subtypes were identified by standardized bioinformatics methods.
transcription profiling by array
Ana Rio-Machin, Bibiana Ferreira, Felipe Prosper, Gonzalo Gómez-López, Joaquín Martínez, Juan C Cigudosa, M J Calasanz, Rafael Fonseca, Sandra Rodriguez-Perales, Sara Alvarez, Travis Henry, Xabier Agirre
Downregulation of specific miRNAs in hyperdiploid multiple myeloma mimics the oncogenic effect of IgH translocations occurring in the non-hyperdiploid subtype. Rio-Machin A, Ferreira BI, Henry T, Gï¿½mez-Lï¿½pez G, Agirre X, Alvarez S, Rodriguez-Perales S, Prosper F, Calasanz MJ, Martï¿½nez J, Fonseca R, Cigudosa JC. , Europe PMC 23174883