MicroRNA transcriptomes of distinct human NK cell populations identify miR-362-5p as an essential regulator of NK cell function
作者单位：Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Life Science and Medical Center University of Science and Technology of China
会议名称：《第十四届全国肿瘤生物治疗大会》
会议日期：2015年
学科分类：1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学]
关 键 词：microRNA transcriptomes natural killer(NK) cells Has-miR-362-5p CYLD NK cell function
摘 要：Background: Natural killer(NK) cells are critical effectors in the immune response against malignancy and infection, and micro RNAs(mi RNAs) play important roles in NK cell biology. However, the micro RNA transcriptomes of the different phenotypes and functions of human NK cell subsets are incompletely understood. Objective: To better understand the physiologic significance of mi RNAs in the regulation of NK cell function. Methods: We examined mi RNA profiles of human NK cells from different cell compartments(peripheral blood, cord blood, and uterine deciduas) and of NKT and T cells from peripheral blood, and highly expressed mi RNAs in human NK cells were identified preferentially. Results: We identified a novel mi RNA, mi R-362-5p, that is highly expressed in human peripheral blood NK(p NK) cells. We also demonstrated that CYLD, a negative regulator of NF-κB signaling, was a target of mi R-362-5p in NK cells. Furthermore, we showed that the over-expression of mi R-362-5p enhanced the expression of IFN-γ, perforin, granzyme-B, and CD107 a in human primary NK cells, and we found that silencing CYLD with a small interfering RNA(si RNA) mirrored the effect of mi R-362-5p over-expression. In contrast, the inhibition of mi R-362-5p had the opposite effect in NK cells, which was abrogated by CYLD si RNA, suggesting that mi R-362-5p promotes NK-cell function, at least in part, by the down-regulation of CYLD. Conclusion: Our results provide a resource for studying the roles of mi RNAs in human NK cell biology and suggest that the modulation of mi R-362-5p may be a useful therapeutic strategy to enhance NK-cell effector function against viral infections and malignancy.