MicroRNA transcriptomes of distinct human NK cell populations identify miR-362-5p as an essential regulator of NK cell function.

Lele Wu,Rui Sun,Sitong Ren,Binqing Fu,Haiming Wei,Yue Yang,Chuang Guo,Zhigang Tian,Fang Ni

doi:10.1038/srep09993

Abstract

Natural killer (NK) cells are critical effectors in the immune response against malignancy and infection, and microRNAs (miRNAs) play important roles in NK cell biology. Here we examined miRNA 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 we identified a novel miRNA, miR-362-5p, that is highly expressed in human peripheral blood NK (pNK) cells. We also demonstrated that CYLD, a negative regulator of NF-κB signaling, was a target of miR-362-5p in NK cells. Furthermore, we showed that the over-expression of miR-362-5p enhanced the expression of IFN-γ, perforin, granzyme-B, and CD107a in human primary NK cells, and we found that silencing CYLD with a small interfering RNA (siRNA) mirrored the effect of miR-362-5p over-expression. In contrast, the inhibition of miR-362-5p had the opposite effect in NK cells, which was abrogated by CYLD siRNA, suggesting that miR-362-5p promotes NK-cell function, at least in part, by the down-regulation of CYLD. These results provide a resource for studying the roles of miRNAs in human NK cell biology and contribute to a better understanding of the physiologic significance of miRNAs in the regulation of NK cell function.

Highlights

MicroRNA transcriptomes of distinct human Natural killer (NK) cell populations identify miR-362-5p as an essential regulator of NK cell function
We showed that the over-expression of miR-362-5p enhanced the expression of IFN-c, perforin, granzyme-B, and CD107a in human primary NK cells, and we found that silencing CYLD with a small interfering RNA mirrored the effect of miR-362-5p over-expression
To further identify novel miRNAs that could provide clues to the differences between the various NK populations, we looked for differential microRNA expression in the different human NK cell populations

Summary

Introduction

MicroRNA transcriptomes of distinct human NK cell populations identify miR-362-5p as an essential regulator of NK cell function. MicroRNAs (miRNAs) are highly conserved small non-coding single-stranded RNA molecules (19–24 nt) that act as key regulators of gene expression at the post-transcriptional level by binding to the 39 untranslated region (UTR) of target mRNAs for translational repression or degradation[17]. These tiny regulators of gene expression have been shown to have unique expression profiles in the cells of the innate and adaptive immune systems and play pivotal roles in the regulation of development and the function of such cells[18,19,20,21,22]. We revealed that endogenous IGF-1 is regulated by miR-483-3p in human NK cells and contributes to NK cell cytotoxicity[29]

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