Lu Shuanglong, Yadav Anil Kumar, Qiao Xiaohong
Department of Pediatrics, Tongji Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Hematology. 2020 Dec;25(1):168-175. doi: 10.1080/16078454.2020.1757332.
MicroRNAs(miRNAs) can regulate T cell differentiation and plasticity by targeting their corresponding message RNAs (mRNAs), which play important roles in many autoimmune diseases. But the effect of miRNAs and their targeted mRNAs in acquired AA is not fully understood. The Gene Expression Omnibus data-sets of bone marrow T cells in acquired AA patients were performed to integrated analysis. Differently expressed miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) were identified. Target mRNAs of DE-miRNAs predicted by miRNet were compared with DE-mRNAs, the intersection mRNAs of two groups were negatively matched with the DE-miRNAs and defined as dysregulated mRNAs. GO and KEGG analyses for dysregulated mRNAs were performed. Protein-protein interaction (PPI) networks for dysregulated mRNAs were established. Modules in the PPI networks were identified, and the miRNA-mRNA networks were constructed. 40 DE-miRNAs and 1511 DE-mRNAs were accessed. 303 negative correlation pairs of miRNA-mRNA were identified. Hsa-mir-34a-5p, hsa-mir-195-5p and hsa-mir-424-5p may be the central hubs. GO and KEGG analyses revealed that dysregulated mRNAs were involved in T cell differentiation and plasticity. Finally, the miRNA-mRNA networks were constructed. Has-mir-34a-5p, hsa-mir-195-5p and hsa-mir-424-5p were all involved in the central network and the target mRNA for them were histone genes and histone methylation gene KMT2D. The miRNA-mRNA network in our study show that hsa-mir-34a-5p, hsa-mir-195-5p, and hsa-mir-424-5p may regulate the T cell differentiation and plasticity by targeting histone gene expression and histone modification.
微小RNA（miRNA）可通过靶向相应的信使RNA（mRNA）来调节T细胞分化和可塑性，这在许多自身免疫性疾病中发挥着重要作用。但miRNA及其靶向mRNA在获得性再生障碍性贫血（AA）中的作用尚未完全明确。我们对获得性AA患者骨髓T细胞的基因表达综合数据库进行了整合分析，鉴定出差异表达的miRNA（DE-miRNA）和mRNA（DE-mRNA）。将通过miRNet预测的DE-miRNA的靶mRNA与DE-mRNA进行比较，两组的交集mRNA与DE-miRNA呈负相关，并定义为失调mRNA。对失调mRNA进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析，建立失调mRNA的蛋白质-蛋白质相互作用（PPI）网络，鉴定PPI网络中的模块，并构建miRNA-mRNA网络。共获得40个DE-miRNA和1511个DE-mRNA，鉴定出303对miRNA-mRNA负相关对。hsa-mir-34a-5p、hsa-mir-195-5p和hsa-mir-424-5p可能是核心枢纽。GO和KEGG分析显示，失调mRNA参与T细胞分化和可塑性。最后构建了miRNA-mRNA网络。Has-mir-34a-5p、hsa-mir-195-5p和hsa-mir-424-5p均参与核心网络，其靶mRNA为组蛋白基因和组蛋白甲基化基因KMT2D。我们研究中的miRNA-mRNA网络表明，hsa-mir-34a-5p、hsa-mir-195-5p和hsa-mir-424-5p可能通过靶向组蛋白基因表达和组蛋白修饰来调节T细胞分化和可塑性。
