MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma

Aldo M. Roccaro, Antonio Sacco, Brian Thompson, Xavier Leleu, Abdel Kareem Azab, Feda Azab, Judith Runnels, Xiaoying Jia, Hai T. Ngo, Molly R. Melhem, Charles P. Lin, Domenico Ribatti, Barrett J. Rollins, Thomas E. Witzig, Kenneth C. Anderson, Irene M. Ghobrial

Research output: Contribution to journalArticle

Abstract

Detailed genomic studies have shown that cytogenetic abnormalities contribute to multiple myeloma (MM) pathogenesis and disease progression. Nevertheless, little is known about the characteristics of MM at the epigenetic level and specifically how microRNAs regulate MM progression in the context of the bone marrow milieu. Therefore, we performed microRNA expression profiling of bone marrow derived CD138+ MM cells versus their normal cellular counterparts and validated data by qRT-PCR. We identified a MM-specific microRNA signature characterized by down-expression of microRNA-15a/-16 and overexpression of microRNA-222/-221/-382/-181a/-181b (P <.01). We investigated the functional role of microRNA-15a and -16 and showed that they regulate proliferation and growth of MM cells in vitro and in vivo by inhibiting AKT serine/threonine-protein-kinase (AKT3), ribosomal-protein-S6, MAP-kinases, and NF-κB-activator MAP3KIP3. Moreover, miRNA-15a and -16 exerted their anti-MM activity even in the context of the bone marrow milieu in vitro and in vivo. These data indicate that microRNAs play a pivotal role in the biology of MM and represent important targets for novel therapies in MM.

Original languageEnglish
Pages (from-to)6669-6680
Number of pages12
JournalBlood
Volume113
Issue number26
DOIs
Publication statusPublished - 2009

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ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Roccaro, A. M., Sacco, A., Thompson, B., Leleu, X., Azab, A. K., Azab, F., Runnels, J., Jia, X., Ngo, H. T., Melhem, M. R., Lin, C. P., Ribatti, D., Rollins, B. J., Witzig, T. E., Anderson, K. C., & Ghobrial, I. M. (2009). MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma. Blood, 113(26), 6669-6680. https://doi.org/10.1182/blood-2009-01-198408