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. 2022 Mar 23;23(7):3469.
doi: 10.3390/ijms23073469.

MicroRNAs in Leukemias: A Clinically Annotated Compendium

Aleksander Turk  1 , George A Calin  2 , Tanja Kunej  1
Affiliations

MicroRNAs in Leukemias: A Clinically Annotated Compendium

Aleksander Turk et al. Int J Mol Sci. .

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.

Keywords: interaction network; leukemia; miRNA-target interaction (MTI); microRNA (miRNA).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Study workflow diagram. * The 248 MTIs in between leukemia-associated miRNAs and target genes are limited to interactions with miRNAs associated with ≥4 leukemia types.
Figure 2
Figure 2
Network of experimentally validated associations between leukemia types and miRNAs. The network contains 137 unique miRNAs associated with 16 types of leukemia, as categorized in miRTarBase. Blue nodes are miRNAs while orange nodes are leukemia types. Each edge represents an experimentally validated association between the miRNA and corresponding leukemia type. A table of data is available in Supplementary Data, Table S1.
Figure 3
Figure 3
Leukemia miRNA-target interaction network. The network contains 127 unique MTIs between 37 leukemia-associated miRNAs and 49 leukemia-associated protein-coding genes. The total number of MTIs in the network is 248. Orange nodes represent miRNA while blue nodes represent target genes. Each edge is an experimentally validated interaction between the miRNA and its target, thus nodes with multiple connecting edges have been validated by multiple experiments.
Figure 4
Figure 4
Network of manually reviewed MTIs identified in leukemia. The network is composed of 10 miRNA-target pairs, 5 sets of interactions between a single miRNA and two or more targets, and a subnetwork consisting of 12 miRNAs and 17 targets. Blue nodes represent miRNAs while orange nodes represent targets. Each edge represents a manually reviewed MTI identified in leukemia cell lines, animal models or patients. Edges do not differentiate between leukemia types. The leukemia type of each MTI is available in Supplementary Data, Table S3.
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