September 15, 2005Proceedings of the National Academy of Sciences3,533 citationsOpen Access
miR-15 and miR-16 induce apoptosis by targeting BCL2
View Full Paper
Key Points
- To investigate whether miR-15a and miR-16-1 regulate the antiapoptotic protein Bcl2 and induce cell death in chronic lymphocytic leukemia.
- Analyzed the relationship between miR-15a/miR-16-1 levels and Bcl2 protein expression in chronic lymphocytic leukemia.
- Evaluated the posttranscriptional repression of Bcl2 and subsequent apoptotic response following microRNA modulation in a leukemic cell line model.
- miR-15a and miR-16-1 expression levels inversely correlate with Bcl2 expression in chronic lymphocytic leukemia.
- Both microRNAs negatively regulate Bcl2 at the posttranscriptional level, and targeted repression of BCL2 triggers apoptosis in leukemic cells.
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.
Cite This Study
Cimmino et al. (2005) studied this question.