Downregulation of specific miRNAs in hyperdiploid multiple myeloma mimics the oncogenic effect of IgH translocations occurring in the non-hyperdiploid subtype

A. Rio-Machin, B. I. Ferreira, T. Henry, G. Gómez-López, X. Agirre, S. Alvarez, S. Rodriguez-Perales, F. Prosper, M. J. Calasanz, J. Martínez, R. Fonseca, J. C. Cigudosa

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)925-931
Number of pages7
JournalLeukemia
Volume27
Issue number4
DOIs
StatePublished - Apr 2013

Keywords

  • aneuploidy
  • chromosomal rearrangements
  • microRNA profile
  • trisomies

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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