<i>miR-15</i> and <i>miR-16</i> induce apoptosis by targeting BCL2

TLDR

Chronic lymphocytic leukemia is marked by malignant B cells that overexpress the anti‑apoptotic protein BCL2, and the microRNAs miR‑15a and miR‑16‑1 are frequently deleted or down‑regulated in these cells. We show that miR‑15a and miR‑16‑1 suppress BCL2 expression post‑transcriptionally, inducing apoptosis in leukemic cells, and suggest they could serve as therapeutic agents against BCL2‑overexpressing tumors.

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.