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Integrated mRNA-microRNA profiling of human NK cell differentiation identifies MiR-583 as a negative regulator of IL2Rγ expression.
- Source :
-
PloS one [PLoS One] 2014 Oct 14; Vol. 9 (10), pp. e108913. Date of Electronic Publication: 2014 Oct 14 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- Natural killer (NK) cells are innate immune effector cells that protect against cancer and some viral infections. Until recently, most studies have investigated the molecular signatures of human or mouse NK cells to identify genes that are specifically expressed during NK cell development. However, the mechanism regulating NK cell development remains unclear. Here, we report a regulatory network of potential interactions during in vitro differentiation of human NK cells, identified using genome-wide mRNA and miRNA databases through hierarchical clustering analysis, gene ontology analysis and a miRNA target prediction program. The microRNA (miR)-583, which demonstrated the largest ratio change in mature NK cells, was highly correlated with IL2 receptor gamma (IL2Rγ) expression. The overexpression of miR-583 had an inhibitory effect on NK cell differentiation. In a reporter assay, the suppressive effect of miR-583 was ablated by mutating the putative miR-583 binding site of the IL2Rγ 3' UTR. Therefore, we show that miR-583 acts as a negative regulator of NK cell differentiation by silencing IL2Rγ. Additionally, we provide a comprehensive database of genome-wide mRNA and miRNA expression during human NK cell differentiation, offering a better understanding of basic human NK cell biology for the application of human NK cells in immunotherapy.
- Subjects :
- 3' Untranslated Regions
Base Sequence
Binding Sites
Cells, Cultured
Cluster Analysis
Databases, Genetic
Fetal Blood cytology
Gene Expression Profiling
Gene Regulatory Networks
Humans
Interleukin Receptor Common gamma Subunit antagonists & inhibitors
Interleukin Receptor Common gamma Subunit genetics
Killer Cells, Natural cytology
Killer Cells, Natural immunology
MicroRNAs genetics
RNA Interference
Sequence Alignment
Cell Differentiation
Down-Regulation
Interleukin Receptor Common gamma Subunit metabolism
Killer Cells, Natural metabolism
MicroRNAs metabolism
RNA, Messenger metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 25313504
- Full Text :
- https://doi.org/10.1371/journal.pone.0108913