Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/22736314http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22736314http://www.w3.org/2000/01/rdf-schema#comment"

Objective

MicroRNAs (miRNAs) function to fine-tune the control of immune cell signaling. It is well established that there are abnormalities in the interleukin-2 (IL-2)-related signaling pathways in systemic lupus erythematosus (SLE). The miR-31 microRNA has been found to be markedly underexpressed in patients with SLE, and thus the present study was undertaken to investigate the role of miR-31 in IL-2 defects in lupus T cells.

Methods

Expression levels of miR-31 were quantitated using TaqMan miRNA assays. Transfection and stimulation of cultured cells followed by TaqMan quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and reporter gene assays were conducted to determine the biologic function of miR-31. NF-AT nuclear translocation and expression were quantitatively measured using an ImageStream cytometer. Bioinformatics analysis, small interfering RNA (siRNA) knockdown, and Western blotting were performed to validate miR-31 targets and effects.

Results

The expression of miR-31 was significantly decreased in lupus T cells, and this was positively correlated with the expression of IL-2. Overexpression of miR-31 in T cells increased the production of IL-2 by altering NF-AT nuclear expression and IL2 promoter activity, while knockdown of endogenous miR-31 reduced IL-2 production. RhoA expression was directly repressed by miR-31 in T cells. Of note, siRNA-mediated knockdown of RhoA enhanced IL2 promoter activity and, consequently, up-regulated IL-2 production. RhoA expression was consistently up-regulated and negatively correlated with the levels of miR-31 in lupus T cells. Manipulation of miR-31 expression in lupus T cells restored the expression of IL-2 at both the messenger RNA and protein levels.

Conclusion

MicroRNA-31 is a novel enhancer of IL-2 production during T cell activation. Dysregulation of miR-31 and its target, RhoA, could be a novel molecular mechanism underlying the IL-2 deficiency in patients with SLE."xsd:string
http://purl.uniprot.org/citations/22736314http://purl.org/dc/terms/identifier"doi:10.1002/art.34596"xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/author"Chen S."xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/author"Huang X."xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/author"Luo X."xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/author"Tang Y."xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/author"Yao Y."xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/author"Fan W."xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/author"Cui H."xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/author"Shen N."xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/author"Higgs B.W."xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/author"Liang D."xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/author"Qu B."xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/author"Jallal B."xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/author"Harley J.B."xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/name"Arthritis Rheum"xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/pages"3715-3725"xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/title"Identification of microRNA-31 as a novel regulator contributing to impaired interleukin-2 production in T cells from patients with systemic lupus erythematosus."xsd:string
http://purl.uniprot.org/citations/22736314http://purl.uniprot.org/core/volume"64"xsd:string
http://purl.uniprot.org/citations/22736314http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22736314
http://purl.uniprot.org/citations/22736314http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/22736314
http://purl.uniprot.org/uniprot/#_Q13169-mappedCitation-22736314http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22736314
http://purl.uniprot.org/uniprot/#_Q71V48-mappedCitation-22736314http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22736314
▶