MicroRNAs in Leukemias: A Clinically Annotated Compendium

Abstract

Leukemias are a group of malignancies of the blood and bone marrow. Multiple types of leukemia are known, however reliable treatments have not been developed for most leukemia types. Furthermore, even relatively reliable treatments can result in relapses. MicroRNAs (miRNAs) are a class of short, noncoding RNAs responsible for epigenetic regulation of gene expression and have been proposed as a source of potential novel therapeutic targets for leukemias. In order to identify central miRNAs for leukemia, we conducted data synthesis using two databases: miRTarBase and DISNOR. A total of 137 unique miRNAs associated with 16 types of leukemia were retrieved from miRTarBase and 86 protein-coding genes associated with leukemia were retrieved from the DISNOR database. Based on these data, we formed a visual network of 248 miRNA-target interactions (MTI) between leukemia-associated genes and miRNAs associated with ≥4 leukemia types. We then manually reviewed the literature describing these 248 MTIs for interactions identified in leukemia studies. This manually curated data was then used to visualize a network of 64 MTIs identified in leukemia patients, cell lines and animal models. We also formed a visual network of miRNA-leukemia associations. Finally, we compiled leukemia clinical trials from the ClinicalTrials database. miRNAs with the highest number of MTIs were miR-125b-5p, miR-155-5p, miR-181a-5p and miR-19a-3p, while target genes with the highest number of MTIs were TP53, BCL2, KIT, ATM, RUNX1 and ABL1. The analysis of 248 MTIs revealed a large, highly interconnected network. Additionally, a large MTI subnetwork was present in the network visualized from manually reviewed data. The interconnectedness of the MTI subnetwork suggests that certain miRNAs represent central disease molecules for multiple leukemia types. Additional studies on miRNAs, their target genes and associated biological pathways are required to elucidate the therapeutic potential of miRNAs in leukemia.

Ikaros Regulates microRNA Networks in Acute Lymphoblastic Leukemia

“…There were 21 upregulated and 10 downregulated DE miRNAs with IK1 expression compared to control. Among the identified IK1-regulated miRNAs, 5/31 unique miRNAs have been previously described as leukemia miRNAs based on their target genes disease assocations [ 30 ]. Interestingly, several IK1-upregulated DE miRNAs have been classified as ‘oncosuppressive’, including hsa-miR-150-3p [ 31 , 32 ], hsa-miR-3663 [ 33 ], and hsa-miR-4497 [ 34 ] ( Figure 2 B).…”

miR-155 and miR-223 as markers of biological and clinical features of chronic lymphocytic leukemia

“…miR-155 представляет собой транскрипт РНК из кластера интеграции В-клеток; обычно miR-155 характеризуют как проонкогенную и провоспалительную микроРНК [19]. miR-155 участвует в регуляции клеточного роста и пролиферации, инвазии, миграции, апоптоза и ангиогенеза при разных видах неоплазий, включая ХЛЛ [19][20][21][22]. Также miR-155 играет важную роль в гемопоэзе и функционировании иммунной системы, в том числе в созревании Т-и В-лимфоцитов и самообновлении гемопоэтических стволовых клеток [20,21].…”

MiRNAs in Hematopoiesis and Acute Lymphoblastic Leukemia

“…In addition, it has been observed that the ectopic expression of let-7c promotes granulocytic differentiation in AML [ 40 ], the low expression of miR-22 modifies the differentiation of monocytes in normal and leukemic states [ 40 ], and changes in the miR-17-92 cluster expression have resulted in the appearance of lymphoproliferative disorders [ 42 ]. A recent study identified miRNAs such as miR-125b-5p, miR-155-5p, miR-181a-5p, and miR-19a-3p and coding genes such as BCL2 , TP53 , KIT , and MYB with the highest number of interactions in several forms of leukemia and other hematological malignancies, including chronic lymphocytic leukemia (CLL) and myelodysplastic syndromes [ 56 ].…”