Transcriptomics,Genomics

Dataset Information

44

MiRNA expression variation in primary NK cells treated with TGF-β1


ABSTRACT: Human NK cells activity against cancer cells is deeply suppressed by TGF-β1, an immunomodulatory cytokine that is released and activated in the tumor microenvironment. Moreover, our previous data showed that TGF-β1 modifies the chemokine receptor repertoire of NK cells. In particular, it decreases the expression of CX3CR1 that drives these effectors toward peripheral tissues, including tumor sites. In order to identify possible mechanisms mediating chemokine receptors modulation, we analyzed the miRNA profile of TGF-β1-treated primary NK cells. The analysis pointed out miR-27a-5p as a possible modulator of CX3CR1. We demonstrated the functional interaction of miR-27a-5p with the 3’ untranslated region (3’UTR) of CX3CR1 mRNA by two different experimental approaches: by the use of a luciferase assay based on a reporter construct containing the CX3CR1 3’UTR and by transfection of primary NK cells with a miR-27a-5p inhibitor. We also showed that the TGF-β1-mediated increase of miR-27a-5p expression is a consequence of miR-23a-27a-24-2 cluster induction. Moreover, we demonstrated that miR-27a-5p down-regulates the surface expression of CX3CR1. Finally we showed that Neuroblastoma cells induced in resting NK cells a downregulation of the CX3CR1 expression that was paralleled by a significant increase of miR-27a-5p expression. Therefore, the present study highlights miR-27a-5p as a pivotal TGF-β1-induced regulator of CX3CR1 expression. Overall design: Real-time PCR-based miRNA expression profiling. Primary resting NK cells from three donors were treated for 24h with 5 or 40 ng/ml TGF-β1 or were left untreated.

INSTRUMENT(S): Applied Biosystems Taqman Low Density Array Human microRNA Card A+B Set v3.0

SUBMITTER: Stefano Regis  

PROVIDER: GSE98769 | GEO | 2017-05-11

SECONDARY ACCESSION(S): PRJNA386164

REPOSITORIES: GEO

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Publications

TGF-β1 Downregulates the Expression of CX3CR1 by Inducing miR-27a-5p in Primary Human NK Cells.

Regis Stefano S   Caliendo Fabio F   Dondero Alessandra A   Casu Beatrice B   Romano Filomena F   Loiacono Fabrizio F   Moretta Alessandro A   Bottino Cristina C   Castriconi Roberta R  

Frontiers in Immunology 20170725


Activity of human natural killer (NK) cells against cancer cells is deeply suppressed by TGF-β1, an immunomodulatory cytokine that is released and activated in the tumor microenvironment. Moreover, our previous data showed that TGF-β1 modifies the chemokine receptor repertoire of NK cells. In particular, it decreases the expression of CX3CR1 that drives these effectors toward peripheral tissues, including tumor sites. To identify possible mechanisms mediating chemokine receptors modulation, we a  ...[more]

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