Integrated analysis of microRNA and transcription factors in the bone marrow of patients with acute monocytic leukemia

Abstract

Acutemonocytic leukemia (AMoL) is a distinct subtype of acute myeloid leukemia (AML) with poor prog- nosis. However, the molecular mechanisms and key regulators involved in the global regulation of gene expression levels in AMoL are poorly understood. In order to elucidate the role of microRNAs (miRNAs/miRs) and transcription factors (TFs) in AMoL pathogenesis at the network level, miRNA and TF expression level profiles were systematically analyzed by miRNA sequencing and TF array, respectively; this identified 285 differentially expressed miRNAs and 139 differentially expressed TFs in AMoL samples compared with controls. By combining expression level profile data and bioinfor- matics tools available for predicting TF and miRNA targets, a comprehensive AMoL-specific miRNA-TF-mediated regulatory network was constructed. A total of 26 miRNAs and 23 TFs were identified as hub nodes in the network. Among these hubs, miR-29b-3p, MYC, TP53 and NFKB1 were determined to be potential AMoL regulators, and were subsequently extracted to construct sub-networks. A hypo- thetical pathway model was also proposed for miR-29b-3p to reveal the potential co-regulatory mechanisms of miR-29b-3p, MYC, TP53 and NFKB1 in AMoL. The present study provided an effective approach to discover critical regulators via a comprehensive regulatory network in AMoL, in addition to enhancing understanding of the pathogenesis of this disease at the molecular level.