Identification of microRNA transcriptome involved in human natural killer cell activation
Identification of microRNA transcriptome involved in human natural killer cell activation
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鉴定参与人类自然杀伤细胞激活的 microRNA 转录组
DOI：
10.1016/j.imlet.2012.02.014
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发表时间：
2012-04-30
影响因子：
4.4
通讯作者：
Yu, Jianxiu
中科院分区：
文献类型：
--
作者：
Liu, Xin;Wang, Yanli;Yu, Jianxiu
自然杀伤（NK）细胞是先天免疫系统的重要组成部分，它识别并杀死病毒感染和恶性细胞。MicroRNA（miRNAs）是一种短的非编码RNA，是免疫细胞基因表达的重要调控因子。然而，对参与人类NK细胞活化的miRNA知之甚少。在这项研究中，我们测序了4个小RNA文库从一个灭活和三个活化的人NK细胞与细胞因子白细胞介素-2（IL-2）处理。使用Illumina高通量测序技术分别检测IL-15和IL-21。我们在静息和IL-2、IL-15和IL-21激活的人NK细胞中分别鉴定了总共940、458、475和452个已知的成熟miRNA。其中，通过实时荧光定量PCR证实了miR-155、miR-15 a、miR-1246和miR-331- 3 p在IL-2、IL-15和IL-21激活的人NK细胞中的差异表达。此外，我们的结果显示，miRNA-155的过度表达增强，而miRNA-155拮抗剂削弱了NK细胞介导的杀伤活性，表明miRNA-155在控制NK细胞的细胞毒性中起着重要作用。这是我们首次发现的参与IL-2、IL-15和IL-21激活人类NK细胞的microRNA转录组和差异表达的miRNAs，为进一步阐明microRNA对人类NK细胞激活的调控提供了有价值的线索，在NK细胞免疫治疗中可能具有巨大的潜力。(c)2012 Elsevier B. V.保留所有权利。
Natural killer (NK) cells are an important component of the innate immune system that recognizes and kills virally infected and malignant cells. MicroRNAs (miRNAs) are short non-coding RNAs that have emerged as critical regulators of gene expression in immune cells. However, very little is known about miRNAs involved in human NK cell activation. In this study, we sequenced 4 small RNA libraries from one inactivated and three activated human NK cells treated with cytokines interleukin-2 (IL-2). IL-15 and IL-21, respectively, by using the Illumina high-throughput sequencing technology. We identified a total of 940, 458, 475 and 452 known mature miRNAs in resting and IL-2, IL-15 and IL-21 activated human NK cells, respectively. Among these, we found a few miRNAs including miR-155, miR-15a, miR-1246 and miR-331-3p with consistent differential expression in all three activated human NK cells by IL-2, IL15 or IL-21, which was confirmed by quantitative real-time PCR. Furthermore, our results revealed that the miRNA-155 over expression enhanced while the miRNA-155 antagonist impaired the NK cell-mediated killing activity, indicating that miRNA-155 plays an important role in the control of NK cell cytotoxicity. This is the first time we showed the microRNA transcriptomes and differentially expressed miRNAs involved in human NK cell activation by IL-2,IL-15 and IL-21 stimulation, which provides valuable clues for the further elucidation of microRNA regulation in human NK cell activation and may have a great potential in NK cell immunotherapy. (c) 2012 Elsevier B.V. All rights reserved.