Department of Animal Science, Biotechnical Faculty, University of Ljubljana, 1230 Domžale, Slovenia.
Department of Translational Molecular Pathology, Division of Pathology, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA.
Int J Mol Sci. 2022 Mar 23;23(7):3469. doi: 10.3390/ijms23073469.
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 and . 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.
白血病是一组血液和骨髓的恶性肿瘤。已知有多种类型的白血病，但对于大多数白血病类型尚未开发出可靠的治疗方法。此外，即使是相对可靠的治疗方法也可能导致复发。微小 RNA（miRNA）是一类短的非编码 RNA，负责基因表达的表观遗传调控，并被提出作为白血病潜在治疗靶点的来源。为了确定白血病的核心 miRNA，我们使用两个数据库进行了数据综合：miRTarBase 和 DISNOR。从 miRTarBase 中检索到与 16 种白血病相关的 137 个独特 miRNA，从 DISNOR 数据库中检索到与白血病相关的 86 个蛋白质编码基因。基于这些数据，我们形成了一个由 248 个 miRNA-靶基因相互作用（MTI）组成的可视化网络，这些相互作用与≥4 种白血病类型相关的 miRNA 和白血病相关基因有关。然后，我们手动审查了描述这些在白血病研究中鉴定的 248 个 MTIs 的文献。然后将经过人工审核的数据用于可视化白血病患者、细胞系和动物模型中鉴定的 64 个 MTIs 的网络。我们还形成了一个 miRNA-白血病关联的可视化网络。最后，我们从 ClinicalTrials 数据库中编译了白血病临床试验。具有最多 MTI 的 miRNA 是 miR-125b-5p、miR-155-5p、miR-181a-5p 和 miR-19a-3p，而具有最多 MTI 的靶基因是 和 。对 248 个 MTIs 的分析显示出一个大型的、高度相互关联的网络。此外，在手动审查数据可视化的网络中存在一个大型的 MTI 子网。MTI 子网的相互连接性表明，某些 miRNA 代表多种白血病类型的核心疾病分子。需要进一步研究 miRNA、其靶基因和相关生物途径，以阐明 miRNA 在白血病中的治疗潜力。
