title: miR-31 regulates interleukin 2 and kinase suppressor of ras 2 during T cell activation.
abstract: MicroRNA (miRNA) has an important role as a master regulator of gene expression in immune system and is upregulated during T cell differentiation, however its function is not clear yet. In this study, the contribution of miR-31 in T cell activation was investigated. miR-31 was upregulated during the activation of primary T lymphocytes upon T-cell receptor (TCR) stimulation. Ectopic expression of miR-31 increased the expression of interleukin (IL)-2, while knockdown of endogenous miR-31 decreased the IL-2 expression. To gain more insights into the regulatory mechanism, we performed a bioinformatic analysis and found miR-31 potentially targeted kinase suppressor of ras 2 (KSR2), a repression factor of Ras2 kinase. Using reporter gene and western blotting assays, we confirmed that miR-31 could inhibit KSR2 by directly targeting its 3' untranslated region (UTR). Moreover, miR-31 enhanced nuclear factor of activated T cells (NF-AT) activity in Jurkat T cells, and increased transcription activity of IL-2 promoter in primary T cells. In conclusion, our study demonstrated that miR-31 upregulated IL-2 expression via reduction of its up-stream kinase suppressor, KSR2, and is a component of T cell activation.
authors.affiliation: Department of Liver Surgery & Liver Transplantation, Shanghai Jiao Tong University School of Medicine, Ren Ji Hospital, Shanghai, China.
authors.forename: F
authors.initials: F
authors.lastname: Xue
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: Y
authors.initials: Y
authors.lastname: Xia
authors.forename: Q
authors.initials: Q
authors.lastname: Xia
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism*; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D007376:Interleukin-2; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D050778:NFATC Transcription Factors; D011948:Receptors, Antigen, T-Cell; C557409:KSR2 protein, human; D017346:Protein Serine-Threonine Kinases