Lin Xiao-Cong, Yang Qin, Fu Wei-Yu, Lan Liu-Bo, Ding Hang, Zhang Yu-Ming, Li Ning, Zhang Hai-Tao
Department of Biochemistry and Molecular Biology, Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China.
Department of Hematology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China.
Oncol Lett. 2021 Jan;21(1):50. doi: 10.3892/ol.2020.12311. Epub 2020 Nov 18.
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, and 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, and 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.
急性单核细胞白血病(AMoL)是急性髓系白血病(AML)的一种独特亚型,预后较差。然而,目前对AMoL中基因表达水平全局调控所涉及的分子机制和关键调节因子了解甚少。为了从网络层面阐明微小RNA(miRNA)和转录因子(TF)在AMoL发病机制中的作用,分别通过miRNA测序和TF阵列系统分析了miRNA和TF的表达水平谱;结果发现与对照相比,AMoL样本中有285个差异表达的miRNA和139个差异表达的TF。通过整合表达水平谱数据和可用于预测TF和miRNA靶标的生物信息学工具,构建了一个全面的AMoL特异性miRNA-TF介导的调控网络。共确定了26个miRNA和23个TF为该网络中的枢纽节点。在这些枢纽中,miR-29b-3p等被确定为潜在的AMoL调节因子,随后被提取出来构建子网。还提出了一个miR-29b-3p的假设通路模型,以揭示miR-29b-3p等在AMoL中的潜在共调节机制。本研究提供了一种通过AMoL中的综合调控网络发现关键调节因子的有效方法,同时增强了对该疾病分子发病机制的理解。