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miR-31 regulates interleukin 2 and kinase suppressor of ras 2 during T cell activation

Genes & Immunity volume 14, pages 127–131 (2013)Cite this article

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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.

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References

  1. Bartel DP . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281–297.

    Article  CAS  Google Scholar 

  2. Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ . Processing of primary microRNAs by the Microprocessor complex. Nature 2004; 432: 231–235.

    Article  CAS  Google Scholar 

  3. Vasudevan S, Tong Y, Steitz JA . Switching from repression to activation: microRNAs can up-regulate translation. Science 2007; 318: 1931–1934.

    Article  CAS  Google Scholar 

  4. Pauley KM, Chan EK . MicroRNAs and their emerging roles in immunology. Ann NY Acad Sci 2008; 1143: 226–239.

    Article  CAS  Google Scholar 

  5. Cobb BS, Nesterova TB, Thompson E, Hertweck A, O'Connor E, Godwin J et al. T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer. J Exp Med 2005; 201: 1367–1373.

    Article  CAS  Google Scholar 

  6. Muljo SA, Ansel KM, Kanellopoulou C, Livingston DM, Rao A, Rajewsky K . Aberrant T cell differentiation in the absence of Dicer. J Exp Med 2005; 202: 261–269.

    Article  CAS  Google Scholar 

  7. Lu LF, Boldin MP, Chaudhry A, Lin LL, Taganov KD, Hanada T et al. Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses. Cell; 142: 914–929.

    Article  CAS  Google Scholar 

  8. Wang S, Tang Y, Cui H, Zhao X, Luo X, Pan W et al. Let-7/miR-98 regulate Fas and Fas-mediated apoptosis. Genes Immun; 12: 149–154.

    Article  Google Scholar 

  9. Li QJ, Chau J, Ebert PJ, Sylvester G, Min H, Liu G et al. miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 2007; 129: 147–161.

    Article  CAS  Google Scholar 

  10. Wu H, Neilson JR, Kumar P, Manocha M, Shankar P, Sharp PA et al. miRNA profiling of naive, effector and memory CD8 T cells. PloS one 2007; 2: e1020.

    Article  Google Scholar 

  11. Lu TX, Hartner J, Lim EJ, Fabry V, Mingler MK, Cole ET et al. MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN-gamma pathway, Th1 polarization, and the severity of delayed-type hypersensitivity. J Immunol 2011; 187: 3362–3373.

    Article  CAS  Google Scholar 

  12. Tang Y, Luo X, Cui H, Ni X, Yuan M, Guo Y et al. MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthritis Rheum 2009; 60: 1065–1075.

    Article  CAS  Google Scholar 

  13. Tenbrock K, Tsokos GC . Transcriptional regulation of interleukin 2 in SLE T cells. Int Rev Immunol 2004; 23: 333–345.

    Article  CAS  Google Scholar 

  14. Rouas R, Fayyad-Kazan H, El Zein N, Lewalle P, Rothe F, Simion A et al. Human natural Treg microRNA signature: role of microRNA-31 and microRNA-21 in FOXP3 expression. Eur J Immunol 2009; 39: 1608–1618.

    Article  CAS  Google Scholar 

  15. Valastyan S, Chang A, Benaich N, Reinhardt F, Weinberg RA . Concurrent suppression of integrin alpha5, radixin, and RhoA phenocopies the effects of miR-31 on metastasis. Cancer Res 2010; 70: 5147–5154.

    Article  CAS  Google Scholar 

  16. Chen C, Rowell EA, Thomas RM, Hancock WW, Wells AD . Transcriptional regulation by Foxp3 is associated with direct promoter occupancy and modulation of histone acetylation. J Biol Chem 2006; 281: 36828–36834.

    Article  CAS  Google Scholar 

  17. Channavajhala PL, Wu L, Cuozzo JW, Hall JP, Liu W, Lin LL et al. Identification of a novel human kinase supporter of Ras (hKSR-2) that functions as a negative regulator of Cot (Tpl2) signaling. J Biol Chem 2003; 278: 47089–47097.

    Article  CAS  Google Scholar 

  18. Gomez-Casero E, San-Antonio B, Iniguez MA, Fresno M . Cot/Tpl2 and PKCzeta cooperate in the regulation of the transcriptional activity of NFATc2 through the phosphorylation of its amino-terminal domain. Cell Signal 2007; 19: 1652–1661.

    Article  CAS  Google Scholar 

  19. Ballester A, Velasco A, Tobena R, Alemany S . Cot kinase activates tumor necrosis factor-alpha gene expression in a cyclosporin A-resistant manner. J Biol Chem 1998; 273: 14099–14106.

    Article  CAS  Google Scholar 

  20. Choi HS, Kang BS, Shim JH, Cho YY, Choi BY, Bode AM et al. Cot, a novel kinase of histone H3, induces cellular transformation through up-regulation of c-fos transcriptional activity. Faseb J 2008; 22: 113–126.

    Article  CAS  Google Scholar 

  21. Gringhuis SI, de Leij LF, Verschuren EW, Borger P, Vellenga E . Interleukin-7 up-regulates the interleukin-2-gene expression in activated human T lymphocytes at the transcriptional level by enhancing the DNA binding activities of both nuclear factor of activated T cells and activator protein-1. Blood 1997; 90: 2690–2700.

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported in part by the Program of the Shanghai Commission of Science and Technology (no.10410701100 and no.09411951800).

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Author notes

  1. F Xue and H Li: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Liver Surgery & Liver Transplantation, Shanghai Jiao Tong University School of Medicine Ren Ji Hospital, Shanghai, China

    F Xue, J Zhang, J Lu, Y Xia & Q Xia

  2. Department of Clinical Laboratory, Shanghai Jiao Tong University School of Medicine Xin Hua Hospital, Shanghai, China

    H Li

  3. Shanghai Institute of Immunology, Shanghai, China

    H Li

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  1. F Xue
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Correspondence to Q Xia.

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Xue, F., Li, H., Zhang, J. et al. miR-31 regulates interleukin 2 and kinase suppressor of ras 2 during T cell activation. Genes Immun 14, 127–131 (2013). https://doi.org/10.1038/gene.2012.58

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