miR-15 and miR-16 induce apoptosis by targeting BCL2

Amelia Cimmino, George Adrian Calin, Muller Fabbri, Marilena V. Iorio, Manuela Ferracin, Masayoshi Shimizu, Sylwia E. Wojcik, Rami I. Aqeilan, Simona Zupo, Mariella Dono, Laura Rassenti, Hansjuerg Alder, Stefano Volinia, Chang Gong Liu, Thomas J. Kipps, Massimo Negrini, Carlo M. Croce

Research output: Contribution to journalArticle

Abstract

Chronic lymphocytic leukemia (CLL) is the most common human leukemia and is characterized by predominantly nondividing malignant B cells overexpressing the antiapoptotic B cell lymphoma 2 (Bcl2) protein. miR-15a and miR-16-1 are deleted or down-regulated in the majority of CLLs. Here, we demonstrate that miR-15a and miR-16-1 expression is inversely correlated to Bcl2 expression in CLL and that both microRNAs negatively regulate Bcl2 at a posttranscriptional level. BCL2 repression by these microRNAs induces apoptopsis in a leukemic cell line model. Therefore, miR-15 and miR-16 are natural antisense Bcl2 interactors that could be used for therapy of Bcl2-overexpressing tumors.

Original languageEnglish
Pages (from-to)13944-13949
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number39
DOIs
Publication statusPublished - Sep 27 2005

Keywords

  • Leukemia
  • MicroRNAs
  • Translation

ASJC Scopus subject areas

  • Genetics
  • General

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  • Cite this

    Cimmino, A., Calin, G. A., Fabbri, M., Iorio, M. V., Ferracin, M., Shimizu, M., Wojcik, S. E., Aqeilan, R. I., Zupo, S., Dono, M., Rassenti, L., Alder, H., Volinia, S., Liu, C. G., Kipps, T. J., Negrini, M., & Croce, C. M. (2005). miR-15 and miR-16 induce apoptosis by targeting BCL2. Proceedings of the National Academy of Sciences of the United States of America, 102(39), 13944-13949. https://doi.org/10.1073/pnas.0506654102