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 prognosis. 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 bioinformatics 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 hypothetical 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.

Cervical Cancer Stem-Like Cell Transcriptome Profiles Predict Response to Chemoradiotherapy

“…Gene Ontology (GO) analysis revealed enrichment of biomolecule synthesis GO terms, where pathways of DNA/ RNA and protein processing, as well as cell metabolism are overrepresented by suppressed genes (Figure 3). This is consistent with previous studies that suggest regulatory gene networks are downregulated in quiescent stem cells in glioblastoma (48) and ovarian cancer (49).…”

The miR-146b-3p/TNFAIP2 axis regulates cell differentiation in acute myeloid leukaemia

“…Acute myeloid leukaemia (AML) refers to a group of blood-forming malignancies that are derived from malignant clones of haematopoietic stem/progenitor cells and characterized by proliferation of bone marrow blasts, inhibition of normal haematopoiesis, and blockade of differentiation [1]. The annual incidence of AML is 0.4 to 2.8 per 100,000, and AML accounts for approximately 40% of leukaemia-related deaths [2][3][4].…”