C/EBP? regulated microRNA-34a targets E2F3 during granulopoiesis and is down-regulated in AML with CEBPA mutations.

ABSTRACT: The transcription factor, CCAAT enhancer binding protein alpha (C/EBP?), is crucial for granulopoiesis and is deregulated by various mechanisms in acute myeloid leukemia (AML). Mutations in the CEBPA gene are reported in 10% of human patients with AML. Even though the C/EBP? mutants are known to display distinct biologic function during leukemogenesis, the molecular basis for this subtype of AML remains elusive. We have recently showed the significance of deregulation of C/EBP?-regulated microRNA (miR) in AML. In this study, we report that miR-34a is a novel target of C/EBP? in granulopoiesis. During granulopoiesis, miR-34a targets E2F3 and blocks myeloid cell proliferation. Analysis of AML samples with CEBPA mutations revealed a lower expression of miR-34a and elevated levels of E2F3 as well as E2F1, a transcriptional target of E2F3. Manipulation of miR-34a reprograms granulocytic differentiation of AML blast cells with CEBPA mutations. These results define miR-34a as a novel therapeutic target in AML with CEBPA mutations.

SUBMITTER: Pulikkan JA 

PROVIDER: S-EPMC3031410 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature