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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3147 Scopus citations


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 languageAmerican English
Pages (from-to)13944-13949
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number39
StatePublished - 27 Sep 2005
Externally publishedYes


  • Leukemia
  • MicroRNAs
  • Translation


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