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Journal of Clinical Immunology

Erschienen in:

01.05.2010

MicroRNA in the Adaptive Immune System, in Sickness and in Health

verfasst von: Adrian Liston, Michelle Linterman, Li-Fan Lu

Erschienen in: Journal of Clinical Immunology | Ausgabe 3/2010

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Abstract

Introduction

MicroRNA are emerging as key regulators of the development and function of adaptive immunity. These 19–24 nucleotide regulatory RNA molecules have essential roles in multiple faucets of adaptive immunity, from regulating the development of the key cellular players to the activation and function in immune responses.

Discussion

MicroRNA are involved in T cell and B cell differentiation in the thymus and bone marrow, and subsequent peripheral homeostasis. The contribution of specific microRNA to the adaptive immune response becomes even more apparent during the effector phases: class switching and germinal centre formation in B cells, differentiation into functional lineages in T cells, and activation of antigen-presentation cells through pattern-recognition pathways. With the capacity of microRNA to alter the survival and death of T and B cells, control over microRNA expression is essential to prevent adaptive immune cells from unregulated proliferation. MicroRNA can act both as ‘oncomirs’ and tumour suppressors, and thus dysregulation of microRNA in lymphocytes can cause malignancies.

Conclusion

In this review, we will describe the role of microRNA in generating a productive adaptive response, and the consequences if microRNA-mediated repression of lymphocytes is perturbed.

Pillai RS, Bhattacharyya SN, Filipowicz W. Repression of protein synthesis by miRNAs: how many mechanisms? Trends Cell Biol. 2007;17:118–26.CrossRefPubMed

Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120:15–20.CrossRefPubMed

Hutvagner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex. Science. 2002;297:2056–60.CrossRefPubMed

Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. 2003;17:3011–6.CrossRefPubMed

Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, et al. Molecular basis for the recognition of primary microRNAs by the Drosha–DGCR8 complex. Cell. 2006;125:887–901.CrossRefPubMed

Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, et al. MicroRNA genes are transcribed by RNA polymerase II. Embo J. 2004;23:4051–60.CrossRefPubMed

Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science. 2004;303:95–8.CrossRefPubMed

Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. Embo J. 2002;21:4663–70.CrossRefPubMed

Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425:415–9.CrossRefPubMed

10.

Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, et al. miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev. 2002;16:720–8.CrossRefPubMed

11.

Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S, Ha I, et al. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell. 2001;106:23–34.CrossRefPubMed

12.

Ketting RF, Fischer SE, Bernstein E, Sijen T, Hannon GJ, Plasterk RH. Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev. 2001;15:2654–9.CrossRefPubMed

13.

Hutvagner G, McLachlan J, Pasquinelli AE, Balint E, Tuschl T, Zamore PD. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 2001;293:834–8.CrossRefPubMed

14.

Lingel A, Simon B, Izaurralde E, Sattler M. Structure and nucleic-acid binding of the Drosophila Argonaute 2 PAZ domain. Nature. 2003;426:465–9.CrossRefPubMed

15.

Bartel DP, Chen CZ. Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs. Nat Rev Genet. 2004;5:396–400.CrossRefPubMed

16.

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;201:1367–73.CrossRefPubMed

17.

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;202:261–9.CrossRefPubMed

18.

Liston A, Lu LF, O’Carroll D, Tarakhovsky A, Rudensky AY. Dicer-dependent microRNA pathway safeguards regulatory T cell function. J Exp Med. 2008;205:1993–2004.CrossRefPubMed

19.

Kosik KS. MicroRNAs tell an evo–devo story. Nat Rev Neurosci. 2009;10:754–9.CrossRefPubMed

20.

Nandi A, Vaz C, Bhattacharya A, Ramaswamy R. miRNA-regulated dynamics in circadian oscillator models. BMC Syst Biol. 2009;3:45.CrossRefPubMed

21.

Wang, X., et al., Toward a system-level understanding of microRNA pathway via mathematical modeling. BioSystems (2009);doi:10.1016/j.biosystems.2009.12.005.

22.

Curtale G, Citarella F, Carissimi C, Goldoni M, Carucci N, Fulci V, et al. An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes. Blood. 2010;115:265–73.CrossRefPubMed

23.

Lu LF, Thai TH, Calado DP, Chaudhry A, Kubo M, Tanaka K, et al. Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity. 2009;30:80–91.CrossRefPubMed

24.

O’Carroll D, Mecklenbrauker I, Das PP, Santana A, Koenig U, Enright AJ, et al. A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway. Genes Dev. 2007;21:1999–2004.CrossRefPubMed

25.

Koralov SB, Muljo SA, Galler GR, Krek A, Chakraborty T, Kanellopoulou C, et al. Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell. 2008;132:860–74.CrossRefPubMed

26.

Ventura A, Young AG, Winslow MM, Lintault L, Meissner A, Erkeland SJ, et al. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell. 2008;132:875–86.CrossRefPubMed

27.

Chen CZ, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science. 2004;303:83–6.CrossRefPubMed

28.

Zhou B, Wang S, Mayr C, Bartel DP, Lodish HF. miR-150, a microRNA expressed in mature B and T cells, blocks early B cell development when expressed prematurely. Proc Natl Acad Sci U S A. 2007;104:7080–5.CrossRefPubMed

29.

Xiao C, Calado DP, Galler G, Thai TH, Patterson HC, Wang J, et al. MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell. 2007;131:146–59.CrossRefPubMed

30.

Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, et al. Regulation of the germinal center response by microRNA-155. Science. 2007;316:604–8.CrossRefPubMed

31.

O’Connell RM, Chaudhuri AA, Rao DS, Baltimore D. Inositol phosphatase SHIP1 is a primary target of miR-155. Proc Natl Acad Sci U S A. 2009;106:7113–8.CrossRefPubMed

32.

Vigorito E, Perks KL, Abreu-Goodger C, Bunting S, Xiang Z, Kohlhaas S, et al. microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells. Immunity. 2007;27:847–59.CrossRefPubMed

33.

Teng G, Hakimpour P, Landgraf P, Rice A, Tuschl T, Casellas R, et al. MicroRNA-155 is a negative regulator of activation-induced cytidine deaminase. Immunity. 2008;28:621–9.CrossRefPubMed

34.

Zhou L, Seo KH, He HZ, Pacholczyk R, Meng DM, Li CG, et al. Tie2cre-induced inactivation of the miRNA-processing enzyme Dicer disrupts invariant NKT cell development. Proc Natl Acad Sci U S A. 2009;106:10266–71.CrossRefPubMed

35.

Fedeli M, Napolitano A, Wong MP, Marcais A, de Lalla C, Colucci F, et al. Dicer-dependent microRNA pathway controls invariant NKT cell development. J Immunol. 2009;183:2506–12.CrossRefPubMed

36.

Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J, et al. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol. 2008;9:405–14.CrossRefPubMed

37.

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;129:147–61.CrossRefPubMed

38.

Ebert PJ, Jiang S, Xie J, Li QJ, Davis MM. An endogenous positively selecting peptide enhances mature T cell responses and becomes an autoantigen in the absence of microRNA miR-181a. Nat Immunol. 2009;10:1162–9.CrossRefPubMed

39.

Yu D, Tan AH, Hu X, Athanasopoulos V, Simpson N, Silva DG, et al. Roquin represses autoimmunity by limiting inducible T-cell co-stimulator messenger RNA. Nature. 2007;450:299–303.CrossRefPubMed

40.

Weitzel RP, Lesniewski ML, Haviernik P, Kadereit S, Leahy P, Greco NJ, et al. microRNA 184 regulates expression of NFAT1 in umbilical cord blood CD4+ T cells. Blood. 2009;113:6648–57.CrossRefPubMed

41.

Cobb BS, Hertweck A, Smith J, O’Connor E, Graf D, Cook T, et al. A role for Dicer in immune regulation. J Exp Med. 2006;203:2519–27.CrossRefPubMed

42.

Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, et al. Requirement of bic/microRNA-155 for normal immune function. Science. 2007;316:608–11.CrossRefPubMed

43.

Stahl HF, Fauti T, Ullrich N, Bopp T, Kubach J, Rust W, et al. miR-155 inhibition sensitizes CD4+ Th cells for TREG mediated suppression. PLoS ONE. 2009;4:e7158.CrossRefPubMed

44.

Du C, Liu C, Kang J, Zhao G, Ye Z, Huang S, et al. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol. 2009;10:1252–9.CrossRefPubMed

45.

Yu D, Rao S, Tsai LM, Lee SK, He Y, Sutcliffe EL, et al. The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity. 2009;31:457–68.CrossRefPubMed

46.

Nurieva RI, Chung Y, Martinez GJ, Yang XO, Tanaka S, Matskevitch TD, et al. Bcl6 mediates the development of T follicular helper cells. Science. 2009;325:1001–5.CrossRefPubMed

47.

Johnston RJ, Poholek AC, DiToro D, Yusuf I, Eto D, Barnett B, et al. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science. 2009;325:1006–10.CrossRefPubMed

48.

Linterman MA, Rigby RJ, Wong RK, Yu D, Brink R, Cannons JL, et al. Follicular helper T cells are required for systemic autoimmunity. J Exp Med. 2009;206:561–76.CrossRefPubMed

49.

Sandberg R, Neilson JR, Sarma A, Sharp PA, Burge CB. Proliferating cells express mRNAs with shortened 3’ untranslated regions and fewer microRNA target sites. Science. 2008;320:1643–7.CrossRefPubMed

50.

Chong MM, Rasmussen JP, Rudensky AY, Littman DR. The RNAseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease. J Exp Med. 2008;205:2005–17.CrossRefPubMed

51.

Zheng Y, Josefowicz SZ, Kas A, Chu TT, Gavin MA, Rudensky AY. Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature. 2007;445:936–40.CrossRefPubMed

52.

Marson A, Kretschmer K, Frampton GM, Jacobsen ES, Polansky JK, MacIsaac KD, et al. Foxp3 occupancy and regulation of key target genes during T-cell stimulation. Nature. 2007;445:931–5.CrossRefPubMed

53.

Zhou X, Jeker LT, Fife BT, Zhu S, Anderson MS, McManus MT, et al. Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J Exp Med. 2008;205:1983–91.CrossRefPubMed

54.

Huang B, Zhao J, Lei Z, Shen S, Li D, Shen GX, et al. miR-142-3p restricts cAMP production in CD4+CD25− T cells and CD4+CD25+ TREG cells by targeting AC9 mRNA. EMBO Rep. 2009;10:180–5.CrossRefPubMed

55.

O’Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A. 2007;104:1604–9.CrossRefPubMed

56.

Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, et al. Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol. 2007;179:5082–9.PubMed

57.

Martinez-Nunez RT, Louafi F, Friedmann PS, Sanchez-Elsner T. MicroRNA-155 modulates the pathogen binding ability of dendritic cells (DCs) by down-regulation of DC-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN). J Biol Chem. 2009;284:16334–42.CrossRefPubMed

58.

Evel-Kabler K, Song XT, Aldrich M, Huang XF, Chen SY. SOCS1 restricts dendritic cells’ ability to break self tolerance and induce antitumor immunity by regulating IL-12 production and signaling. J Clin Invest. 2006;116:11.

59.

Androulidaki A, Iliopoulos D, Arranz A, Doxaki C, Schworer S, Zacharioudaki V, et al. The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs. Immunity. 2009;31:220–31.CrossRefPubMed

60.

Ceppi M, Pereira PM, Dunand-Sauthier I, Barras E, Reith W, Santos MA, et al. MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells. Proc Natl Acad Sci U S A. 2009;106:2735–40.CrossRefPubMed

61.

Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A. 2006;103:12481–6.CrossRefPubMed

62.

Hou J, Wang P, Lin L, Liu X, Ma F, An H, et al. MicroRNA-146a feedback inhibits RIG-I-dependent Type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. J Immunol. 2009;183:2150–8.CrossRefPubMed

63.

Nahid MA, Pauley KM, Satoh M, Chan EK. miR-146a is critical for endotoxin-induced tolerance: implication in innate immunity. J Biol Chem. 2009;284:34590–9.CrossRefPubMed

64.

Liu G, Friggeri A, Yang Y, Park YJ, Tsuruta Y, Abraham E. miR-147, a microRNA that is induced upon Toll-like receptor stimulation, regulates murine macrophage inflammatory responses. Proc Natl Acad Sci U S A. 2009;106:15819–24.CrossRefPubMed

65.

Sheedy FJ, Palsson-McDermott E, Hennessy EJ, Martin C, O’Leary JJ, Ruan Q, et al. Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol. 2010;11:141–7.CrossRefPubMed

66.

Roehle A, Hoefig KP, Repsilber D, Thorns C, Ziepert M, Wesche KO, et al. MicroRNA signatures characterize diffuse large B-cell lymphomas and follicular lymphomas. Br J Haematol. 2008;142:732–44.CrossRefPubMed

67.

Marcucci G, Radmacher MD, Maharry K, Mrozek K, Ruppert AS, Paschka P, et al. MicroRNA expression in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358:1919–28.CrossRefPubMed

68.

Garzon R, Calin GA, Croce CM. MicroRNAs in cancer. Annu Rev Med. 2009;60:167–79.CrossRefPubMed

69.

Havelange V, Garzon R, Croce CM. MicroRNAs: new players in acute myeloid leukaemia. Br J Cancer. 2009;101:743–8.CrossRefPubMed

70.

Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101:2999–3004.CrossRefPubMed

71.

He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, et al. A microRNA polycistron as a potential human oncogene. Nature. 2005;435:828–33.CrossRefPubMed

72.

Tagawa H, Seto M. A microRNA cluster as a target of genomic amplification in malignant lymphoma. Leukemia. 2005;19:2013–6.CrossRefPubMed

73.

Inomata M, Tagawa H, Guo YM, Kameoka Y, Takahashi N, Sawada K. MicroRNA-17-92 down-regulates expression of distinct targets in different B-cell lymphoma subtypes. Blood. 2009;113:396–402.CrossRefPubMed

74.

Olive V, Bennett MJ, Walker JC, Ma C, Jiang I, Cordon-Cardo C, et al. miR-19 is a key oncogenic component of mir-17-92. Genes Dev. 2009;23:2839–49.CrossRefPubMed

75.

Mu P, Han YC, Betel D, Yao E, Squatrito M, Ogrodowski P, et al. Genetic dissection of the miR-17 92 cluster of microRNAs in Myc-induced B-cell lymphomas. Genes Dev. 2009;23:2806–11.CrossRefPubMed

76.

Eis PS, Tam W, Sun L, Chadburn A, Li Z, Gomez MF, et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci U S A. 2005;102:3627–32.CrossRefPubMed

77.

Kluiver J, Poppema S, de Jong D, Blokzijl T, Harms G, Jacobs S, et al. BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas. J Pathol. 2005;207:243–9.CrossRefPubMed

78.

van den Berg A, Kroesen BJ, Kooistra K, de Jong D, Briggs J, Blokzijl T, et al. High expression of B-cell receptor inducible gene BIC in all subtypes of Hodgkin lymphoma. Genes Chromosomes Cancer. 2003;37:20–8.CrossRefPubMed

79.

Metzler M, Wilda M, Busch K, Viehmann S, Borkhardt A. High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma. Genes Chromosomes Cancer. 2004;39:167–9.CrossRefPubMed

80.

Costinean S, Sandhu SK, Pedersen IM, Tili E, Trotta R, Perrotti D, et al. Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein beta are targeted by miR-155 in B cells of Emicro-MiR-155 transgenic mice. Blood. 2009;114:1374–82.CrossRefPubMed

81.

Costinean S, Zanesi N, Pekarsky Y, Tili E, Volinia S, Heerema N, et al. Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice. Proc Natl Acad Sci U S A. 2006;103:7024–9.CrossRefPubMed

82.

Yamanaka Y, Tagawa H, Takahashi N, Watanabe A, Guo YM, Iwamoto K, et al. Aberrant overexpression of microRNAs activate AKT signaling via down-regulation of tumor suppressors in natural killer-cell lymphoma/leukemia. Blood. 2009;114:3265–75.CrossRefPubMed

83.

Fulci V, Chiaretti S, Goldoni M, Azzalin G, Carucci N, Tavolaro S, et al. Quantitative technologies establish a novel microRNA profile of chronic lymphocytic leukemia. Blood. 2007;109:4944–51.CrossRefPubMed

84.

Lawrie CH, Soneji S, Marafioti T, Cooper CD, Palazzo S, Paterson JC, et al. MicroRNA expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma. Int J Cancer. 2007;121:1156–61.CrossRefPubMed

85.

Navarro A, Gaya A, Martinez A, Urbano-Ispizua A, Pons A, Balague O, et al. MicroRNA expression profiling in classic Hodgkin lymphoma. Blood. 2008;111:2825–32.CrossRefPubMed

86.

Bullrich F, Fujii H, Calin G, Mabuchi H, Negrini M, Pekarsky Y, et al. Characterization of the 13q14 tumor suppressor locus in CLL: identification of ALT1, an alternative splice variant of the LEU2 gene. Cancer Res. 2001;61:6640–8.PubMed

87.

Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002;99:15524–9.CrossRefPubMed

88.

Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005;102:13944–9.CrossRefPubMed

89.

Scaglione BJ, Salerno E, Balan M, Coffman F, Landgraf P, Abbasi F, et al. Murine models of chronic lymphocytic leukaemia: role of microRNA-16 in the New Zealand Black mouse model. Br J Haematol. 2007;139:645–57.CrossRefPubMed

90.

Pekarsky Y, Santanam U, Cimmino A, Palamarchuk A, Efanov A, Maximov V, et al. Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res. 2006;66:11590–3.CrossRefPubMed

91.

Garzon R, Heaphy CE, Havelange V, Fabbri M, Volinia S, Tsao T, et al. MicroRNA 29b functions in acute myeloid leukemia. Blood. 2009;114:5331–41.CrossRefPubMed

92.

Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, et al. MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood. 2009;113:6411–8.CrossRefPubMed

93.

He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007;447:1130–4.CrossRefPubMed

94.

Pigazzi M, Manara E, Baron E, Basso G. miR-34b targets cyclic AMP-responsive element binding protein in acute myeloid leukemia. Cancer Res. 2009;69:2471–8.CrossRefPubMed

95.

Zenz T, Habe S, Denzel T, Mohr J, Winkler D, Buhler A, et al. Detailed analysis of p53 pathway defects in fludarabine-refractory chronic lymphocytic leukemia (CLL): dissecting the contribution of 17p deletion, TP53 mutation, p53-p21 dysfunction, and miR34a in a prospective clinical trial. Blood. 2009;114:2589–97.PubMed

Titel: MicroRNA in the Adaptive Immune System, in Sickness and in Health
verfasst von: Adrian Liston
Michelle Linterman
Li-Fan Lu
Publikationsdatum: 01.05.2010
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 3/2010
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-010-9378-5

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MicroRNA in the Adaptive Immune System, in Sickness and in Health

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Introduction

Discussion

Conclusion

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