HDAC2-dependent miRNA signature in acute myeloid leukemia

Acute myeloid leukemia (AML) is a multifactorial and highly heterogeneous malignancy, whose incidence rises with age. Among the many epigenetic regulators, histone deacetylases are tightly involved in AML etiology. Notably, HDAC2 is highly overexpressed in solid and haematological cancers, including AML. HDAC2 silencing by enzymatic inhibition has a substantial impact on leukemia cell proliferation and immune regulation, as described in our previous work (Conte M. et al. doi:10.18632/oncotarget.2816). Altered miRNAs in AML are known to play a critical role in a broad range of key molecular processes via sophisticated regulation of distinct targets, orchestrating a molecular intracellular balance of gene expression. Recently, the potential use of circulating miRNAs as biomarkers for AML diagnosis/prognosis and as therapeutic targets has been widely explored, and many miRNAs were found to be associated with HDAC2 dysfunction in leukemia. Here, we identified a cluster of common up- and downregulated miRNAs in both SAHA-treated and HDAC2-downregulated cells. By miRNA target network computational analysis, we defined an HDAC2mediated miRNA signatures in AML by genetic and enzymatic HDAC2 deficiency in a U937 leukemic cell line. We propose a crucial role of miR-96-5p and miR92a-3p and related target genes and their relationship with HDAC2 in AML. This HDAC2-dependent miRNA signature in AML highlights the potentially beneficial effects of treatment with epigenetic drugs alone or in combination with other therapies.