title: Downregulation of specific miRNAs in hyperdiploid multiple myeloma mimics the oncogenic effect of IgH translocations occurring in the non-hyperdiploid subtype.
abstract: Currently, multiple myeloma (MM) patients are broadly grouped into a non-hyperdiploid (nh-MM) group, highly enriched for IgH translocations, or into a hyperdiploid (h-MM) group, which is typically characterized by trisomies of some odd-numbered chromosomes. We compared the micro RNA (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 D 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.
authors.affiliation: Molecular Cytogenetics Group, Human Cancer Genetics Program, Centro Nacional Investigaciones Oncológicas (CNIO), Calle Melchor Fernández Almagro 3, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Rio-Machin
authors.forename: B I
authors.initials: BI
authors.lastname: Ferreira
authors.forename: T
authors.initials: T
authors.lastname: Henry
authors.forename: G
authors.initials: G
authors.lastname: Gómez-López
authors.forename: X
authors.initials: X
authors.lastname: Agirre
authors.forename: S
authors.initials: S
authors.lastname: Alvarez
authors.forename: S
authors.initials: S
authors.lastname: Rodriguez-Perales
authors.forename: F
authors.initials: F
authors.lastname: Prosper
authors.forename: M J
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: J
authors.initials: J
authors.lastname: Martínez
authors.forename: R
authors.initials: R
authors.lastname: Fonseca
authors.forename: J C
authors.initials: JC
authors.lastname: Cigudosa
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D019175:DNA Methylation; D017931:DNA Primers; D004171:Diploidy; D015536:Down-Regulation; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D009101:Multiple Myeloma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
chemical_list: D017931:DNA Primers; D007143:Immunoglobulin Heavy Chains; D035683:MicroRNAs