Identification of microRNA transcriptome involved in human natural killer cell activation.
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 440, 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 them iRNA-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.
Lab of Tumor Suppressor Genes and MiRNAs, Institute of Medical Science, Shanghai Jiao-Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
Xin
X
Liu
Yanli
Y
Wang
Qian
Q
Sun
Jie
J
Yan
Jian
J
Huang
Shiguo
S
Zhu
Jianxiu
J
Yu
D002460:Cell Line; D016000:Cluster Analysis; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D059467:Transcriptome
D016207:Cytokines; C524942:MIRN155 microRNA, human; D035683:MicroRNAs