MicroRNAs, new effectors and regulators of NF-κB

Immunological Reviews

Volumn 246, Issue 1, 2012, Pages 205-220

  Boldin, Mark P ^a   Baltimore, David ^b  

^a CITY OF HOPE NATIONAL MEDICAL CENTER   (United States)

^b CALIFORNIA INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Autoimmunity; Cancer; Inflammation; MiRNA; NF B

Indexed keywords

B LYMPHOCYTE RECEPTOR; BRCA1 PROTEIN; CHEMOKINE RECEPTOR CXCR4; FAS ASSOCIATED DEATH DOMAIN PROTEIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERFERON REGULATORY FACTOR 5; INTERLEUKIN 1 RECEPTOR ASSOCIATED KINASE 1; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 4; MICRORNA; MICRORNA 146A; MICRORNA 146ALPHA; MICRORNA 155; MICRORNA 21; MICRORNA 301A; MICRORNA 9; MITOGEN ACTIVATED PROTEIN KINASE; MYELOID DIFFERENTIATION FACTOR 88; RNA; SMAD4 PROTEIN; STAT1 PROTEIN; STAT3 PROTEIN; STRESS ACTIVATED PROTEIN KINASE; TUMOR NECROSIS FACTOR; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6; UNCLASSIFIED DRUG; UNTRANSLATED RNA;

3' UNTRANSLATED REGION; ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; ARTICLE; AUTOIMMUNITY; DISEASE PREDISPOSITION; DNA BINDING; EPIGENETICS; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE LOCUS; GENETIC ASSOCIATION; GENETIC TRANSCRIPTION; HUMAN; IMMUNE RESPONSE; INFLAMMATION; LEARNING; LYMPHOMA; MEMORY; MYELODYSPLASTIC SYNDROME; NEGATIVE FEEDBACK; NONHUMAN; POSITIVE FEEDBACK; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SYSTEMIC LUPUS ERYTHEMATOSUS; TRANSCRIPTION INITIATION; UPREGULATION;

ANIMALS; GENE EXPRESSION REGULATION; HUMANS; INFLAMMATION; MICRORNAS; NF-KAPPA B; SIGNAL TRANSDUCTION;

EID: 84858722006     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/j.1600-065X.2011.01089.x     Document Type: Article

References (172)

1. Ambros V. The functions of animal microRNAs. Nature 2004;431:350-355.
2. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116:281-297.
3. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 2010;11:597-610.
4. Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol 2009;10:126-139.
5. Cifuentes D, et al. A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity. Science 2010;328:1694-1698.
6. Cheloufi S, Dos Santos CO, Chong MM, Hannon GJ. A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature 2010;465:584-589.
7. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009;136:215-233.
8. Chiang HR, et al. Mammalian microRNAs: experimental evaluation of novel and previously annotated genes. Genes Dev 2010;24:992-1009.
9. Monticelli S, et al. MicroRNA profiling of the murine hematopoietic system. Genome Biol 2005;6:R71.
10. Chen CZ, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science 2004;303:83-86.
11. 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;205:2005-2017.
12. Zhou X, et al. Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J Exp Med 2008;205:1983-1991.
13. Koralov SB, et al. Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell 2008;132:860-874.
14. Xiao C, Rajewsky K. MicroRNA control in the immune system: basic principles. Cell 2009;136:26-36.
15. O'Connell RM, Zhao JL, Rao DS. MicroRNA function in myeloid biology. Blood 2011;118:2960-2969.
16. O'Connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol 2010;10:111-122.
17. Pedersen I, David M. MicroRNAs in the immune response. Cytokine 2008;43:391-394.
18. Lindsay MA. microRNAs and the immune response. Trends Immunol 2008;29:343-351.
19. Sen R. The origins of NF-kappaB. Nat Immunol 2011;12:686-688.
20. Queen C, Baltimore D. Immunoglobulin gene transcription is activated by downstream sequence elements. Cell 1983;33:741-748.
21. Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 1986;46:705-716.
22. Staudt LM, Singh H, Sen R, Wirth T, Sharp PA, Baltimore D. A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes. Nature 1986;323:640-643.
23. Murre C, McCaw PS, Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD and myc proteins. Cell 1989;56:777-783.
24. Baeuerle PA, Baltimore D. Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-κB transcription factor. Cell 1988;53:211-217.
25. Ghosh S, Gifford AM, Riviere LR, Tempst P, Nolan GP, Baltimore D. Cloning of the p50 DNA binding subunit of NF-κB: Homology to rel and dorsal. Cell 1990;62:1019-1029.
26. Nolan GP, Ghosh S, Liou H-C, Tempst P, Baltimore D. DNA binding and IκB inhibition of the cloned p65 subunit of NF-κB, a rel-related polypeptide. Cell 1991;64:961-969.
27. Chen IS, Wilhelmsen KC, Temin HM. Structure and expression of c-rel, the cellular homolog to the oncogene of reticuloendotheliosis virus strain T. J Virol 1983;45:104-1013.
28. Steward R. Dorsal, an embryonic polarity gene in Drosophila, is homologous to the vertebrate proto-oncogene, c-rel. Science 1987;238:692-694.
29. Nabel G, Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature 1987;326:711-713.
30. Inlay MA, Tian H, Lin T, Xu Y. Important roles for E protein binding sites within the immunoglobulin κ chain intronic enhancer in activating Vκ Jκ rearrangement. J Exp Med 2004;200:1205-1211.
31. Lee RC FR, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993;75:843-854.
32. Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 1993;75:855-862.
33. 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;103:12481-12486.
34. Kluiver J, et al. Regulation of pri-microRNA BIC transcription and processing in Burkitt lymphoma. Oncogene 2007;26:3769-3776.
35. Impey S, et al. Defining the CREB regulon: a genome-wide analysis of transcription factor regulatory regions. Cell 2004;119:1041-1054.
36. Bazzoni F, et al. Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals. Proc Natl Acad Sci U S A 2009;106:5282-5387.
37. Sheedy FJ, et al. Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol 2010;11:141-147.
38. 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;106:15819-15824.
39. Boldin MP, et al. miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J Exp Med 2011;208:1189-1201.
40. Kuchen S, et al. Regulation of microRNA expression and abundance during lymphopoiesis. Immunity 2010;32:828-839.
41. Starczynowski DT, et al. MicroRNA-146a disrupts hematopoietic differentiation and survival. Exp Hematol 2011;39:167-178.
42. Cameron JE, et al. Epstein-Barr virus latent membrane protein 1 induces cellular microRNA miR-146a, a modulator of lymphocyte signaling pathways. J Virol 2008;82:1946-1958.
43. Larner-Svensson HM, et al. Pharmacological studies of the mechanism and function of interleukin-1beta-induced miRNA-146a expression in primary human airway smooth muscle. Respir Res 2010;11:68.
44. Curtale G, 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;115:265-273.
45. Heinz S, Glass CK. Roles of lineage-determining transcription factors in establishing open chromatin: lessons from high-throughput studies. Curr Top Microbiol Immunol 2012;356:1-16.
46. Hou J, et al. MicroRNA-146a feedback inhibits RIG-I-dependent type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. J Immunol 2009;183:2150-2158.
47. Ghani S, et al. Macrophage development from HSCs requires PU.1-coordinated microRNA expression. Blood 2011;118:2275-2284.
48. Jurkin J, et al. miR-146a is differentially expressed by myeloid dendritic cell subsets and desensitizes cells to TLR2-dependent activation. J Immunol 2010;184:4955-4965.
49. Luo X, et al. A functional variant in microRNA-146a promoter modulates its expression and confers disease risk for systemic lupus erythematosus. PLoS Genet 2011;7:e1002128.
50. Chang TC, et al. Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet 2008;40:43-50.
51. Labbaye C, et al. A three-step pathway comprising PLZF/miR-146a/CXCR4 controls megakaryopoiesis. Nat Cell Biol 2008;10:788-801.
52. Nikiforova MN, Tseng GC, Steward D, Diorio D, Nikiforov YE. MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility. J Clin Endocrinol Metab 2008;93:1600-1608.
53. Xia H, et al. microRNA-146b inhibits glioma cell migration and invasion by targeting MMPs. Brain Res 2009;1269:158-165.
54. Raponi M, et al. MicroRNA classifiers for predicting prognosis of squamous cell lung cancer. Cancer Res 2009;69:5776-5783.
55. Perry MM, Williams AE, Tsitsiou E, Larner-Svensson HM, Lindsay MA. Divergent intracellular pathways regulate interleukin-1beta-induced miR-146a and miR-146b expression and chemokine release in human alveolar epithelial cells. FEBS Lett 2009;583:3349-3355.
56. Clurman BE, Hayward WS. Multiple proto-oncogene activations in avian leukosis virus-induced lymphomas: evidence for stage-specific events. Mol Cell Biol 1989;9:2657-2664.
57. Tam W, Ben-Yehuda D, Hayward WS. bic, a novel gene activated by proviral insertions in avian leukosis virus-induced lymphomas, is likely to function through its noncoding RNA. Mol Cell Biol 1997;17:1490-1502.
58. 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;104:1604-1609.
59. Thai TH, et al. Regulation of the germinal center response by microRNA-155. Science 2007;316:604-608.
60. Lam LT, et al. Compensatory IKKalpha activation of classical NF-kappaB signaling during IKKbeta inhibition identified by an RNA interference sensitization screen. Proc Natl Acad Sci U S A 2008;105:20798-20803.
61. Eis PS, et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci U S A 2005;102:3627-3632.
62. Kluiver J, et al. BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas. J Pathol 2005;207:243-249.
63. Yin Q, Wang X, McBride J, Fewell C, Flemington E. B-cell receptor activation induces BIC/miR-155 expression through a conserved AP-1 element. J Biol Chem 2008;283:2654-2662.
64. Gatto G, Rossi A, Rossi D, Kroening S, Bonatti S, Mallardo M. Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-kappaB pathway. Nucleic Acids Res 2008;36:6608-6619.
65. 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;445:936-940.
66. Lu LF, et al. Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity 2009;30:80-91.
67. McCoy CE, et al. IL-10 inhibits miR-155 induction by toll-like receptors. J Biol Chem 2010;285:20492-20498.
68. Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 2005;65:6029-6033.
69. Volinia S, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 2006;103:2257-2261.
70. Connolly E, et al. Elevated expression of the miR-17-92 polycistron and miR-21 in hepadnavirus-associated hepatocellular carcinoma contributes to the malignant phenotype. Am J Pathol 2008;173:856-864.
71. Iorio MV, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005;65:7065-7070.
72. Fujita S, et al. miR-21 Gene expression triggered by AP-1 is sustained through a double-negative feedback mechanism. J Mol Biol 2008;378:492-504.
73. Loffler D, et al. Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. Blood 2007;110:1330-1333.
74. Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 2004;10:1957-1966.
75. Iliopoulos D, Jaeger SA, Hirsch HA, Bulyk ML, Struhl K. STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol Cell 2010;39:493-506.
76. Lu Z, et al. miR-301a as an NF-kappaB activator in pancreatic cancer cells. EMBO J 2011;30:57-67.
77. Hanisch A, Sillje HH, Nigg EA. Timely anaphase onset requires a novel spindle and kinetochore complex comprising Ska1 and Ska2. EMBO J 2006;25:5504-5515.
78. Lee EJ, et al. Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer 2007;120:1046-1054.
79. + T-cell activation, migration, and survival. Proc Natl Acad Sci U S A 2010;107:21629-21634.
80. Jeffrey PL, et al. CROC-4: a novel brain specific transcriptional activator of c-fos expressed from proliferation through to maturation of multiple neuronal cell types. Mol Cell Neurosci 2000;16:185-196.
81. Zhou J, et al. A novel gene, NMES1, downregulated in human esophageal squamous cell carcinoma. Int J Cancer 2002;101:311-316.
82. Monk CE, Hutvagner G, Arthur JS. Regulation of miRNA transcription in macrophages in response to Candida albicans. PLoS ONE 2010;5:e13669.
83. O'Hara SP, et al. NFkappaB p50-CCAAT/enhancer-binding protein beta (C/EBPbeta)-mediated transcriptional repression of microRNA let-7i following microbial infection. J Biol Chem 2010;285:216-225.
84. Zhou R, Hu G, Liu J, Gong AY, Drescher KM, Chen XM. NF-kappaB p65-dependent transactivation of miRNA genes following Cryptosporidium parvum infection stimulates epithelial cell immune responses. PLoS Pathog 2009;5:e1000681.
85. Zhou R, Hu G, Gong AY, Chen XM. Binding of NF-kappaB p65 subunit to the promoter elements is involved in LPS-induced transactivation of miRNA genes in human biliary epithelial cells. Nucleic Acids Res 2010;38:3222-3232.
86. Liew FY, Xu D, Brint EK, O'Neill LA. Negative regulation of toll-like receptor-mediated immune responses. Nat Rev Immunol 2005;5:446-458.
87. Inoue J, Gohda J, Akiyama T. Characteristics and biological functions of TRAF6. Adv Exp Med Biol 2007;597:72-79.
88. Flannery S, Bowie AG. The interleukin-1 receptor-associated kinases: critical regulators of innate immune signalling. Biochem Pharmacol 2010;80:1981-1991.
89. Yang K, et al. MiR-146a inhibits oxidized low-density lipoprotein-induced lipid accumulation and inflammatory response via targeting toll-like receptor 4. FEBS Lett 2011;585:854-860.
90. Lu L-F, et al. Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses. Cell 2010;142:914-929.
91. Tang 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.
92. Garcia AI, et al. Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers. EMBO Mol Med 2011;3:279-290.
93. Lin SL, Chiang A, Chang D, Ying SY. Loss of mir-146a function in hormone-refractory prostate cancer. RNA 2008;14:417-424.
94. Zhong H, et al. Targeting Smad4 links microRNA-146a to the TGF-beta pathway during retinoid acid induction in acute promyelocytic leukemia cell line. Int J Hematol 2010;92:129-135.
95. Perry MM, Moschos SA, Williams AE, Shepherd NJ, Larner-Svensson HM, Lindsay MA. Rapid changes in microRNA-146a expression negatively regulate the IL-1beta-induced inflammatory response in human lung alveolar epithelial cells. J Immunol 2008;180:5689-5698.
96. Pauley KM, et al. Formation of GW/P bodies as marker for microRNA-mediated regulation of innate immune signaling in THP-1 cells. Immunol Cell Biol 2010;88:205-212.
97. Opalinska JB, et al. MicroRNA expression in maturing murine megakaryocytes. Blood 2010;116:e128-138.
98. Nakasa T, et al. Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum 2008;58:1284-1292.
99. Niimoto T, et al. MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients. BMC Musculoskelet Disord 2010;11:209.
100. Sonkoly E, et al. MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? PLoS ONE 2007;2:e610.
101. Pauley KM, et al. Altered miR-146a expression in Sjogren's syndrome and its functional role in innate immunity. Eur J Immunol 2011;41:2029-2039.
102. Li D, et al. Genetic study of two single nucleotide polymorphisms within corresponding microRNAs and susceptibility to tuberculosis in a Chinese Tibetan and Han population. Hum Immunol 2011;72:598-602.
103. Rioux JD, et al. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat Genet 2001;29:223-228.
104. Kauppi P, et al. A second-generation association study of the 5q31 cytokine gene cluster and the interleukin-4 receptor in asthma. Genomics 2001;77:35-42.
105. Nahid MA, Pauley KM, Satoh M, Chan EK. miRNA-146a is critical for endotoxin-induced tolerance. Implication on innate immunity. J Biol Chem 2009;284:34590-34599.
106. El Gazzar M, Church A, Liu T, McCall CE. MicroRNA-146a regulates both transcription silencing and translation disruption of TNF-α during TLR4-induced gene reprogramming. J Leukoc Biol 2011;90:509-519.
107. Beeson PB. Tolerance to bacterial pyrogens: I. Factors influencing its development. J Exp Med 1947;86:29-38.
108. Beeson PB. Tolerance to bacterial pyrogens: II. Role of the reticulo-endothelial system. J Exp Med 1947;86:39-44.
109. Foster SL, Hargreaves DC, Medzhitov R. Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 2007;447:972-978.
110. Chen X, El Gazzar M, Yoza BK, McCall CE. The NF-kappaB factor RelB and histone H3 lysine methyltransferase G9a directly interact to generate epigenetic silencing in endotoxin tolerance. J Biol Chem 2009;284:27857-27865.
111. Zhao JL, Rao DS, Boldin MP, Taganov KD, O'Connell RM, Baltimore D. NF-kappaB dysregulation in microRNA-146a-deficient mice drives the development of myeloid malignancies. Proc Natl Acad Sci U S A 2011;108:9184-9189.
112. Starczynowski DT, et al. Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype. Nat Med 2010;16:49-58.
113. Wang Y, et al. MicroRNAs expression signatures are associated with lineage and survival in acute leukemias. Blood Cells Mol Dis 2010;44:191-197.
114. Kumar MS, et al. Coordinate loss of a microRNA and protein-coding gene cooperate in the pathogenesis of 5q- syndrome. Blood 2011;118:4666-4673.
115. Paik JH, et al. MicroRNA-146a downregulates NFkappaB activity via targeting TRAF6 and functions as a tumor suppressor having strong prognostic implications in NK/T cell lymphoma. Clin Cancer Res 2011;17:4761-4771.
116. Hou Z, Xie L, Yu L, Qian X, Liu B. MicroRNA-146a is down-regulated in gastric cancer and regulates cell proliferation and apoptosis. Med Oncol 2011;DOI:10.1007/s12032-011-9862-7.
117. Tchernitsa O, et al. Systematic evaluation of the miRNA-ome and its downstream effects on mRNA expression identifies gastric cancer progression. J Pathol 2010;222:310-319.
118. Yue C, et al. Polymorphism of the pre-miR-146a is associated with risk of cervical cancer in a Chinese population. Gynecol Oncol 2011;122:33-37.
119. Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci U S A 2008;105:7269-7274.
120. Ben-Neriah Y, Karin M. Inflammation meets cancer, with NF-kappaB as the matchmaker. Nat Immunol 2011;12:715-723.
121. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008;454:436-444.
122. Rodriguez A, et al. Requirement of bic/microRNA-155 for normal immune function. Science 2007;316:608-611.
123. Vigorito E, et al. microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells. Immunity 2007;27:847-859.
124. Dorsett Y, et al. MicroRNA-155 suppresses activation-induced cytidine deaminase-mediated Myc-Igh translocation. Immunity 2008;28:630-638.
125. Teng G, et al. MicroRNA-155 is a negative regulator of activation-induced cytidine deaminase. Immunity 2008;28:621-629.
126. O'Connell RM, et al. MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity 2010;33:607-619.
127. Bluml S, et al. Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice. Arthritis Rheum 2011;63:1281-1288.
128. Kohlhaas S, Garden OA, Scudamore C, Turner M, Okkenhaug K, Vigorito E. Cutting edge: the Foxp3 target miR-155 contributes to the development of regulatory T cells. J Immunol 2009;182:2578-2582.
129. O'Connell RM, et al. Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder. J Exp Med 2008;205:585-594.
130. 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;106:7113-7118.
131. Wang P, et al. Inducible microRNA-155 feedback promotes type I IFN signaling in antiviral innate immunity by targeting suppressor of cytokine signaling 1. J Immunol 2010;185:6226-6233.
132. Androulidaki A, et al. The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs. Immunity 2009;31:220-231.
133. Costinean S, 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;103:7024-7029.
134. Garzon R, Croce CM. MicroRNAs in normal and malignant hematopoiesis. Curr Opin Hematol 2008;15:352-358.
135. Herranz H, Cohen SM. MicroRNAs and gene regulatory networks: managing the impact of noise in biological systems. Genes Dev 2010;24:1339-1344.
136. Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP. The impact of microRNAs on protein output. Nature 2008;455:64-71.
137. Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N. Widespread changes in protein synthesis induced by microRNAs. Nature 2008;455:58-63.
138. Cmarik JL, et al. Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation. Proc Natl Acad Sci U S A 1999;96:14037-14042.
139. Shibahara K, Asano M, Ishida Y, Aoki T, Koike T, Honjo T. Isolation of a novel mouse gene MA-3 that is induced upon programmed cell death. Gene 1995;166:297-301.
140. Loh PG, et al. Structural basis for translational inhibition by the tumour suppressor Pdcd4. EMBO J 2009;28:274-285.
141. Yang HS, et al. The transformation suppressor Pdcd4 is a novel eukaryotic translation initiation factor 4A binding protein that inhibits translation. Mol Cell Biol 2003;23:26-37.
142. Hilliard A, et al. Translational regulation of autoimmune inflammation and lymphoma genesis by programmed cell death 4. J Immunol 2006;177:8095-8102.
143. Lu TX, Munitz A, Rothenberg ME. MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression. J Immunol 2009;182:4994-5002.
144. Lu TX, et al. MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN-γ pathway, Th1 polarization, and the severity of delayed-type hypersensitivity. J Immunol 2011;187:3362-3373.
145. Marquez RT, Wendlandt E, Galle CS, Keck K, McCaffrey AP. MicroRNA-21 is upregulated during the proliferative phase of liver regeneration, targets Pellino-1, and inhibits NF-kappaB signaling. Am J Physiol Gastrointest Liver Physiol 2010;298:G535-G541.
146. Karin M. NF-kappaB and cancer: mechanisms and targets. Mol Carcinog 2006;45:355-361.
147. Selcuklu SD, Donoghue MT, Spillane C. miR-21 as a key regulator of oncogenic processes. Biochem Soc Trans 2009;37:918-925.
148. Medina PP, Nolde M, Slack FJ. OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature 2010;467:86-90.
149. Iliopoulos D, Hirsch HA, Struhl K. An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 2009;139:693-706.
150. Nourbakhsh M, Hauser H. Constitutive silencing of IFN-beta promoter is mediated by NRF (NF-kappaB-repressing factor), a nuclear inhibitor of NF-kappaB. EMBO J 1999;18:6415-6425.
151. Nourbakhsh M, Kalble S, Dorrie A, Hauser H, Resch K, Kracht M. The NF-kappa b repressing factor is involved in basal repression and interleukin (IL)-1-induced activation of IL-8 transcription by binding to a conserved NF-kappa b-flanking sequence element. J Biol Chem 2001;276:4501-4508.
152. Feng X, et al. Identification of a negative response element in the human inducible nitric-oxide synthase (hiNOS) promoter: the role of NF-kappa B-repressing factor (NRF) in basal repression of the hiNOS gene. Proc Natl Acad Sci U S A 2002;99:14212-14217.
153. Froese N, et al. Innate immune responses in NF-kappaB-repressing factor-deficient mice. Mol Cell Biol 2006;26:293-302.
154. Leucht C, Stigloher C, Wizenmann A, Klafke R, Folchert A, Bally-Cuif L. MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary. Nat Neurosci 2008;11:641-648.
155. Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol 2009;1:a000034.
156. Wang B, et al. TGFbeta-mediated upregulation of hepatic miR-181b promotes hepatocarcinogenesis by targeting TIMP3. Oncogene 2010;29:1787-1797.
157. Shi L, et al. hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells. Brain Res 2008;1236:185-193.
158. Chen R, et al. Regulation of IKKbeta by miR-199a affects NF-kappaB activity in ovarian cancer cells. Oncogene 2008;27:4712-4723.
159. Lee YB, Bantounas I, Lee DY, Phylactou L, Caldwell MA, Uney JB. Twist-1 regulates the miR-199a/214 cluster during development. Nucleic Acids Res 2009;37:123-128.
160. Yin G, et al. TWISTing stemness, inflammation and proliferation of epithelial ovarian cancer cells through MIR199A2/214. Oncogene 2010;29:3545-3553.
161. Song L, et al. miR-218 inhibits the invasive ability of glioma cells by direct downregulation of IKK-beta. Biochem Biophys Res Commun 2010;402:135-140.
162. Fang Y, Shi C, Manduchi E, Civelek M, Davies PF. MicroRNA-10a regulation of proinflammatory phenotype in athero-susceptible endothelium in vivo and in vitro. Proc Natl Acad Sci U S A 2010;107:13450-13455.
163. Sun SC. Non-canonical NF-kappaB signaling pathway. Cell Res 2011;21:71-85.
164. Li T, Morgan MJ, Choksi S, Zhang Y, Kim YS, Liu ZG. MicroRNAs modulate the noncanonical transcription factor NF-kappaB pathway by regulating expression of the kinase IKKalpha during macrophage differentiation. Nat Immunol 2010;11:799-805.
165. Hercus TR, et al. The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease. Blood 2009;114:1289-1298.
166. Prosser HM, Koike-Yusa H, Cooper JD, Law FC, Bradley A. A resource of vectors and ES cells for targeted deletion of microRNAs in mice. Nat Biotechnol 2011;29:850-850.
167. Johnnidis JB, et al. Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature 2008;451:1125-1129.
168. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 2009;11:228-234.
169. Saj A, Lai EC. Control of microRNA biogenesis and transcription by cell signaling pathways. Curr Opin Genet Dev 2011;21:504-510.
170. Guttman M, et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 2009;458:223-227.
171. Bertone P, et al. Global identification of human transcribed sequences with genome tiling arrays. Science 2004;306:2242-2246.
172. Kapranov P, et al. Large-scale transcriptional activity in chromosomes 21 and 22. Science 2002;296:916-919.