Haematology Unit, Cancer Research Centre, Institute for Medical Research, Jalan Pahang, Kuala Lumpur, Malaysia.
Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Genet Test Mol Biomarkers. 2021 Mar;25(3):199-210. doi: 10.1089/gtmb.2020.0182.
The association between dysregulated microRNAs (miRNAs) and acute myeloid leukemia (AML) is well known. However, our understanding of the regulatory role of miRNAs in the cytogenetically normal AML (CN-AML) subtype pathway is still poor. The current study integrated miRNA and mRNA profiles to explore novel miRNA-mRNA interactions that affect the regulatory patterns of CN-AML. We utilized a multiplexed nanoString nCounter platform to profile both miRNAs and mRNAs using similar sets of patient samples ( = 24). Correlations were assessed, and an miRNA-mRNA network was constructed. The underlying biological functions of the mRNAs were predicted by gene enrichment. Finally, the interacting pairs were assessed using TargetScan and microT-CDS. We identified 637 significant negative correlations (false discovery rate <0.05). Network analysis revealed a cluster of 12 miRNAs representing the majority of mRNA targets. Within the cluster, five miRNAs (miR-495-3p, miR-185-5p, let-7i-5p, miR-409-3p, and miR-127-3p) were posited to play a pivotal role in the regulation of CN-AML, as they are associated with the negative regulation of myeloid leukocyte differentiation, negative regulation of myeloid cell differentiation, and positive regulation of hematopoiesis. Three novel interactions in CN-AML were predicted as let-7i-5p:, miR-495-3p:, and miR-495-3p: may be responsible for regulating myeloid cell differentiation in CN-AML.
miRNAs 失调与急性髓系白血病(AML)之间的关联是众所周知的。然而,我们对 miRNA 在核型正常 AML(CN-AML)亚型途径中的调节作用的理解仍然有限。本研究整合了 miRNA 和 mRNA 谱,以探索影响 CN-AML 调节模式的新型 miRNA-mRNA 相互作用。我们使用多重纳米 String nCounter 平台,使用相似的患者样本集(n=24)对 miRNA 和 mRNA 进行分析。评估了相关性,并构建了 miRNA-mRNA 网络。通过基因富集预测了 mRNAs 的潜在生物学功能。最后,使用 TargetScan 和 microT-CDS 评估了相互作用对。我们确定了 637 个显著负相关(错误发现率<0.05)。网络分析显示,有 12 个 miRNA 簇代表了大多数 mRNA 靶标。在该簇中,有五个 miRNA(miR-495-3p、miR-185-5p、let-7i-5p、miR-409-3p 和 miR-127-3p)被认为在 CN-AML 的调节中起着关键作用,因为它们与髓样白细胞分化的负调节、髓样细胞分化的负调节和造血的正调节有关。在 CN-AML 中预测了三个新的相互作用,即 let-7i-5p:、miR-495-3p:和 miR-495-3p:可能负责调节 CN-AML 中的髓样细胞分化。