Sexual dimorphism of miRNA expression: A new perspective in understanding the sex bias of autoimmune diseases

Therapeutics and Clinical Risk Management

Volumn 10, Issue 1, 2014, Pages 151-163

  Dai, Rujuan ^a   Ansar Ahmed, S ^a  

^a VIRGINIA MARYLAND REGIONAL COLLEGE OF VETERINARY MEDICINE   (United States)

Author keywords

Autoimmune diseases; Immune regulation; MicroRNA; Sex differences; Sex hormones; X chromosome

Indexed keywords

ANDROGEN; ARGONAUTE 2 PROTEIN; CD40 LIGAND; CYCLIN DEPENDENT KINASE INHIBITOR 1B; CYTOCHROME P450 2B9; DICER; DNA DIRECTED RNA POLYMERASE III; ESTROGEN; ESTROGEN RECEPTOR ALPHA; EXPORTIN 5; INTERLEUKIN 10; MICRORNA; MICRORNA 127; MICRORNA 155; MICRORNA 182; MICRORNA 221; MICRORNA 222; MICRORNA 223; MICRORNA 23A; MICRORNA 31; MICRORNA 379; MICRORNA 98; RIBONUCLEASE III; RNA POLYMERASE II; RNASE III ENZYME DROSHA; SINGLE STRANDED RNA; TOLL LIKE RECEPTOR 7; UNCLASSIFIED DRUG; X CHROMOSOME LINKED MICRORNA; X LINKED INHIBITOR OF APOPTOSIS;

3' UNTRANSLATED REGION; AUTOIMMUNE DISEASE; AUTOIMMUNITY; BIOGENESIS; CAUSE OF DEATH; CD4+ T LYMPHOCYTE; CELLULAR DISTRIBUTION; DISEASE PREDISPOSITION; DISEASE SEVERITY; EPIGENETICS; GENDER BIAS; GENE; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE LOCATION; GENE TARGETING; GENETIC PREDISPOSITION; GENETIC TRANSCRIPTION; GONAD DEVELOPMENT; GONAD FUNCTION; HORMONAL REGULATION; HUMAN; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; IMMUNOLOGICAL TOLERANCE; IMMUNOREGULATION; MIRTRON; MOLECULAR RECOGNITION; NONHUMAN; PATHOPHYSIOLOGY; REGULATORY T LYMPHOCYTE; REVIEW; RNA STRUCTURE; SEX DETERMINATION; SEX DIFFERENCE; SEX DIFFERENTIATION; SEX RATIO; SIGNAL TRANSDUCTION; SYSTEMIC LUPUS ERYTHEMATOSUS; TISSUE DISTRIBUTION; X CHROMOSOME INACTIVATION; XIAP GENE; Y CHROMOSOME;

EID: 84897832523     PISSN: 11766336     EISSN: 1178203X     Source Type: Journal    
DOI: 10.2147/TCRM.S33517     Document Type: Review

References (151)

1. Ansar Ahmed S, Hissong BD, Verthelyi D, Donner K, Becker K, Karpuzoglu-Sahin E. Gender and risk of autoimmune diseases: possible role of estrogenic compounds. Environ Health Perspect. 1999; 107 Suppl 5:681-686.
2. Ansar Ahmed S, Penhale WJ, Talal N. Sex hormones, immune responses, and autoimmune diseases. Mechanisms of sex hormone action. Am J Pathol. 1985;121(3):531-551.
3. Whitacre CC. Sex differences in autoimmune disease. Nat Immunol. 2001;2(9):777-780.
4. Klein SL. Immune cells have sex and so should journal articles. Endocrinology. 2012;153(6):2544-2550.
5. Shapira Y, Agmon-Levin N, Shoenfeld Y. Defining and analyzing geoepidemiology and human autoimmunity. J Autoimmun. 2010;34(3): J168-J17.
6. National Institutes of Health, Autoimmune Disease Coordinating Committee. Progress in Autoimmune Disease Research. Bethesda, MD: National Institutes of Health; 2005. Available from: http://www.niaid.nih.gov/topics/autoimmune/documents/adccfinal.pdf. Accessed March 2005.
7. Walsh SJ, Rau LM. Autoimmune diseases: a leading cause of death among young and middle-aged women in the United States. Am J Public Health. 2000;90(9):1463-1466.
8. Strickland FM, Hewagama A, Lu Q, et al. Environmental exposure, estrogen and two X chromosomes are required for disease development in an epigenetic model of lupus. J Autoimmun. 2012;38(2-3):J135-J143.
9. Invernizzi P, Pasini S, Selmi C, Gershwin ME, Podda M. Female predominance and X chromosome defects in autoimmune diseases. J Autoimmun. 2009;33(1):12-16.
10. Libert C, Dejager L, Pinheiro I. The X chromosome in immune functions: when a chromosome makes the difference. Nat Rev Immunol. 2010;10(8):594-604.
11. Lamason R, Zhao P, Rawat R, et al. Sexual dimorphism in immune response genes as a function of puberty. BMC Immunol. 2006;7:2.
12. Bernstein E, Kim SY, Carmell MA, et al. Dicer is essential for mouse development. Nat Genet. 2003;35(3):215-217.
13. Dai R, Ansar Ahmed S. MicroRNA, a new paradigm for understanding immunoregulation, inflammation, and autoimmune diseases. Transl Res. 2011;157(4):163-179.
14. Baltimore D, Boldin MP, O'Connell RM, Rao DS, Taganov KD. MicroRNAs: new regulators of immune cell development and function. Nat Immunol. 2008;9(8):839-845.
15. Zhang B, Pan X, Cobb GP, Anderson TA. microRNAs as oncogenes and tumor suppressors. Dev Biol. 2007;302(1):1-12.
16. Dai R, Zhang Y, Khan D, et al. Identification of a common lupus disease-associated microRNA expression pattern in three different murine models of lupus. PLoS One. 2010;5(12):e14302.
17. Shen N, Liang D, Tang Y, de Vries N, Tak PP. MicroRNAs-novel regulators of systemic lupus erythematosus pathogenesis. Nat Rev Rheumatol. 2012;8(12):701-709.
18. Alevizos I, Illei GG. MicroRNAs in Sjögren's syndrome as a prototypic autoimmune disease. Autoimmun Rev. 2010;9(9):618-621.
19. Ceribelli A, Yao B, Dominguez-Gutierrez PR, Nahid MA, Satoh M, Chan EK. MicroRNAs in systemic rheumatic diseases. Arthritis Res Ther. 2011;13(4):229.
20. Du C, Liu C, Kang J, et al. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol. 2009;10(12):1252-1259.
21. Ode F Jr, Moore CS, Kennedy TE, Antel JP, Bar-Or A, Dhaunchak AS. MicroRNA dysregulation in multiple sclerosis. Front Genet. 2013;3:311.
22. Dai R, McReynolds S, Leroith T, Heid B, Liang Z, Ansar Ahmed S. Sex differences in the expression of lupus-associated miRNAs in splenocytes from lupus-prone NZB/WF1 mice. Biol Sex Differ. 2013;4(1):19.
23. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A. Identification of mammalian microRNA host genes and transcription units. Genome Res. 2004;14(10A):1902-1910.
24. Kim VN, Nam JW. Genomics of microRNA. Trends Genet. 2006;22(3): 165-173.
25. Gregory RI, Yan KP, Amuthan G, et al. The Microprocessor complex mediates the genesis of microRNAs. Nature. 2004;432(7014): 235-240.
26. Lee Y, Ahn C, Han J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425(6956):415-419.
27. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281-297.
28. Ruby JG, Jan CH, Bartel DP. Intronic microRNA precursors that bypass Drosha processing. Nature. 2007;448(7149):83-86.
29. Okamura K, Hagen JW, Duan H, Tyler DM, Lai EC. The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell. 2007;130(1):89-100.
30. Berezikov E, Chung WJ, Willis J, Cuppen E, Lai EC. Mammalian mirtron genes. Mol Cell. 2007;28(2):328-336.
31. 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(1):15-20.
32. Baek D, Villén J, Shin C, Camargo FD, Gygi SP, Bartel DP. The impact of microRNAs on protein output. Nature. 2008;455(7209):64-71.
33. Selbach M, Schwanhäusser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N. Widespread changes in protein synthesis induced by microRNAs. Nature. 2008;455(7209):58-63.
34. Vasudevan S, Tong Y, Steitz JA. Switching from repression to activation: microRNAs can up-regulate translation. Science. 2007; 318(5858):1931-1934.
35. Da Sacco L, Masotti A. Recent Insights and Novel Bioinformatics Tools to Understand the Role of MicroRNAs Binding to 5′ Untranslated Region. Int J Mol Sci. 2012;14(1):480-495.
36. Lee I, Ajay SS, Yook JI, et al. New class of microRNA targets containing simultaneous 5′-UTR and 3′-UTR interaction sites. Genome Res. 2009;19(7):1175-1183.
37. Engels BM, Hutvagner G. Principles and effects of microRNA-mediated post-transcriptional gene regulation. Oncogene. 2006;25(46): 6163-6169.
38. Griffiths-Jones S. The microRNA Registry. Nucleic Acids Res. 2004; 32(Database issue):D109-D111.
39. Miranda KC, Huynh T, Tay Y, et al. A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell. 2006;126(6):1203-1217.
40. O'Connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol. 2010;10(2):111-122.
41. Krützfeldt J, Stoffel M. MicroRNAs: a new class of regulatory genes affecting metabolism. Cell Metab. 2006;4(1):9-12.
42. Zhang B, Farwell MA. microRNAs: a new emerging class of players for disease diagnostics and gene therapy. J Cell Mol Med. 2008;12(1): 3-21.
43. Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010;101(10):2087-2092.
44. van Rooij E, Purcell AL, Levin AA. Developing microRNA therapeutics. Circ Res. 2012;110(3):496-507.
45. Cobb BS, Nesterova TB, Thompson E, et al. T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer. J Exp Med. 2005;201(9):1367-1373.
46. Koralov SB, Muljo SA, Galler GR, et al. Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage. Cell. 2008;132(5):860-874.
47. 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(9):2005-2017.
48. 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(2):261-269.
49. Zhou X, Jeker LT, Fife BT, et al. Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J Exp Med. 2008;205(9): 1983-1991.
50. 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(9):1993-2004.
51. Cobb BS, Hertweck A, Smith J, et al. A role for Dicer in immune regulation. J Exp Med. 2006;203(11):2519-2527.
52. Taganov KD, Boldin MP, Baltimore D. MicroRNAs and immunity: tiny players in a big field. Immunity. 2007;26(2):133-137.
53. Lodish HF, Zhou B, Liu G, Chen CZ. Micromanagement of the immune system by microRNAs. Nat Rev Immunol. 2008;8(2):120-130.
54. Gantier MP, Sadler AJ, Williams BR. Fine-tuning of the innate immune response by microRNAs. Immunol Cell Biol. 2007;85(6):458-462.
55. Sonkoly E, Ståhle M, Pivarcsi A. MicroRNAs and immunity: novel players in the regulation of normal immune function and inflammation. Semin Cancer Biol. 2008;18(2):131-140.
56. Lu LF, Boldin MP, Chaudhry A, et al. Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses. Cell. 2010;142(6): 914-829.
57. Rodriguez A, Vigorito E, Clare S, et al. Requirement of bic/microRNA-155 for normal immune function. Science. 2007;316(5824):608-611.
58. O'Connell RM, Kahn D, Gibson WS, et al. MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity. 2010;33(4):607-619.
59. Li QJ, Chau J, Ebert PJ, et al. miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell. 2007;129(1):147-161.
60. Xiao C, Srinivasan L, Calado DP, et al. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol. 2008;9(4):405-414.
61. Stittrich AB, Haftmann C, Sgouroudis E, et al. The microRNA miR-182 is induced by IL-2 and promotes clonal expansion of activated helper T lymphocytes. Nat Immunol. 2010;11(11):1057-1062.
62. 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(33):12481-12486.
63. Thai TH, Calado DP, Casola S, et al. Regulation of the germinal center response by microRNA-155. Science. 2007;316(5824):604-608.
64. Marriott I, Huet-Hudson YM. Sexual dimorphism in innate immune responses to infectious organisms. Immunol Res. 2006;34(3):177-192.
65. Ansar Ahmed S, Karpuzoglu E, Khan D. Effects of sex steroids on innate and adaptive immunity. In: Klein SL, Roberts CW, editors. Sex Hormones and Immunity to Infection. Berlin: Springer-Verlag; 2010:19-52.
66. Ross MT, Grafham DV, Coffey AJ, et al. The DNA sequence of the human X chromosome. Nature. 2005;434(7031):325-337.
67. Wilhelm D, Koopman P. The makings of maleness: towards an integrated view of male sexual development. Nat Rev Genet. 2006;7(8): 620-631.
68. Wijchers PJ, Festenstein RJ. Epigenetic regulation of autosomal gene expression by sex chromosomes. Trends Genet. 2011;27(4):132-140.
69. Fish EN. The X-files in immunity: sex-based differences predispose immune responses. Nat Rev Immunol. 2008;8(9):737-744.
70. Carrel L, Willard HF. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature. 2005;434(7031): 400-404.
71. García-Ortiz H, Velázquez-Cruz R, Espinosa-Rosales F, Jiménez-Morales S, Baca V, Orozco L. Association of TLR7 copy number variation with susceptibility to childhood-onset systemic lupus erythematosus in Mexican population. Ann Rheum Dis. 2010;69(10):1861-1865.
72. Shen N, Fu Q, Deng Y, et al. Sex-specific association of X-linked Toll-like receptor 7 (TLR7) with male systemic lupus erythematosus. Proc Natl Acad Sci U S A. 2010;107(36):15838-15843.
73. Lu Q, Wu A, Tesmer L, Ray D, Yousif N, Richardson B. Demethylation of CD40LG on the inactive X in T cells from women with lupus. J Immunol. 2007;179(9):6352-6358.
74. Morgan CP, Bale TL. Sex differences in microRNA regulation of gene expression: no smoke, just miRs. Biol Sex Differ. 2012;3(1):22.
75. Hossain MM, Ghanem N, Hoelker M, et al. Identification and characterization of miRNAs expressed in the bovine ovary. BMC Genomics. 2009;10:443.
76. Juanchich A, Le Cam A, Montfort J, Guiguen Y, Bobe J. Identification of differentially expressed miRNAs and their potential targets during fish ovarian development. Biol Reprod. 2013;88(5):128.
77. Mishima T, Takizawa T, Luo SS, et al. MicroRNA (miRNA) cloning analysis reveals sex differences in miRNA expression profiles between adult mouse testis and ovary. Reproduction. 2008;136(6):811-822.
78. Ro S, Park C, Sanders KM, McCarrey JR, Yan W. Cloning and expression profiling of testis-expressed microRNAs. Dev Biol. 2007;311(2): 592-602.
79. Ro S, Song R, Park C, Zheng H, Sanders KM, Yan W. Cloning and expression profiling of small RNAs expressed in the mouse ovary. RNA. 2007;13(12):2366-2380.
80. Torley KJ, da Silveira JC, Smith P, et al. Expression of miRNAs in ovine fetal gonads: potential role in gonadal differentiation. Reprod Biol Endocrinol. 2011;9:2.
81. Bannister SC, Tizard ML, Doran TJ, Sinclair AH, Smith CA. Sexually dimorphic microRNA expression during chicken embryonic gonadal development. Biol Reprod. 2009;81(1):165-176.
82. Yang Q, Hua J, Wang L, et al. MicroRNA and piRNA profiles in normal human testis detected by next generation sequencing. PLoS One. 2013;8(6):e66809.
83. Li M, Liu Y, Wang T, et al. Repertoire of porcine microRNAs in adult ovary and testis by deep sequencing. Int J Biol Sci. 2011;7(7):1045-1055.
84. Cheung L, Gustavsson C, Norstedt G, Tollet-Egnell P. Sex-different and growth hormone-regulated expression of microRNA in rat liver. BMC Mol Biol. 2009;10:13.
85. Mujahid S, Logvinenko T, Volpe MV, Nielsen HC. miRNA regulated pathways in late stage murine lung development. BMC Dev Biol. 2013;13:13.
86. Pak TR, Rao YS, Prins SA, Mott NN. An emerging role for microRNAs in sexually dimorphic neurobiological systems. Pflugers Arch. 2013; 465(5):655-667.
87. Ziats MN, Rennert OM. Identification of differentially expressed microRNAs across the developing human brain. Mol Psychiatry. Epub August 6, 2013.
88. Morgan CP, Bale TL. Early prenatal stress epigenetically programs dysmasculinization in second-generation offspring via the paternal lineage. J Neurosci. 2011;31(33):11748-11755.
89. Koturbash I, Zemp F, Kolb B, Kovalchuk O. Sex-specific radiation-induced microRNAome responses in the hippocampus, cerebellum and frontal cortex in a mouse model. Mutat Res. 2011;722(2):114-118.
90. Siegel C, Li J, Liu F, Benashski SE, McCullough LD. miR-23a regulation of X-linked inhibitor of apoptosis (XIAP) contributes to sex differences in the response to cerebral ischemia. Proc Natl Acad Sci U S A. 2011;108(28):11662-11667.
91. Xie X, Miao L, Yao J, et al. Role of multiple microRNAs in the sexually dimorphic expression of Cyp2b9 in mouse liver. Drug Metab Dispos. 2013;41(10):1732-1737.
92. Freitak D, Knorr E, Vogel H, Vilcinskas A. Gender-and stressor-specific microRNA expression in Tribolium castaneum. Biol Lett. 2012;8(5):860-863.
93. Ceribelli A, Satoh M, Chan EK. MicroRNAs and autoimmunity. Curr Opin Immunol. 2012;24(6):686-691.
94. Pauley KM, Cha S, Chan EK. MicroRNA in autoimmunity and autoimmune diseases. J Autoimmun. 2009;32(3-4):189-194.
95. Pan W, Zhu S, Yuan M, et al. MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1. J Immunol. 2010;184(12):6773-6781.
96. Rouas R, Fayyad-Kazan H, El Zein N, et al. Human natural Treg microRNA signature: role of microRNA-31 and microRNA-21 in FOXP3 expression. Eur J Immunol. 2009;39(6):1608-1618.
97. Fan W, Liang D, Tang Y, et al. Identification of microRNA-31 as a novel regulator contributing to impaired interleukin-2 production in T cells from patients with systemic lupus erythematosus. Arthritis Rheum. 2012;64(11):3715-3725.
98. Vigorito E, Perks KL, Abreu-Goodger C, et al. microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells. Immunity. 2007;27(6):847-859.
99. 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(5):1604-1609.
100. Kurowska-Stolarska M, Alivernini S, Ballantine LE, et al. MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis. Proc Natl Acad Sci U S A. 2011;108(27):11193-11198.
101. Leng RX, Pan HF, Qin WZ, Chen GM, Ye DQ. Role of microRNA-155 in autoimmunity. Cytokine Growth Factor Rev. 2011;22(3):141-147.
102. Divekar AA, Dubey S, Gangalum PR, Singh RR. Dicer insufficiency and microRNA-155 overexpression in lupus regulatory T cells: an apparent paradox in the setting of an inflammatory milieu. J Immunol. 2011;186(2):924-930.
103. Xie T, Liang J, Liu N, et al. MicroRNA-127 inhibits lung inflammation by targeting IgG Fcγ receptor I. J Immunol. 2012;188(5):2437-2444.
104. Pinheiro I, Dejager L, Libert C. X-chromosome-located microRNAs in immunity: might they explain male/female differences? The X chromosome-genomic context may affect X-located miRNAs and downstream signaling, thereby contributing to the enhanced immune response of females. Bioessays. 2011;33(11):791-802.
105. Hewagama A. Role of X-Chromosome encoded miRNAs in autoimmunity: suppressing the suppressor and female predisposition. Rheumatol Curr Res. 2013;3(1):118.
106. Fazi F, Rosa A, Fatica A, et al. A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell. 2005;123(5):819-831.
107. Johnnidis JB, Harris MH, Wheeler RT, et al. Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature. 2008;451(7182):1125-1129.
108. Pulikkan JA, Dengler V, Peramangalam PS, et al. Cell-cycle regulator E2F1 and microRNA-223 comprise an autoregulatory negative feedback loop in acute myeloid leukemia. Blood. 2010;115(9): 1768-1778.
109. Stamatopoulos B, Meuleman N, Haibe-Kains B, et al. microRNA-29c and microRNA-223 down-regulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification. Blood. 2009;113(21):5237-5245.
110. Wong QW, Lung RW, Law PT, et al. MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1. Gastroenterology. 2008;135(1):257-269.
111. Fulci V, Scappucci G, Sebastiani GD, et al. miR-223 is overexpressed in T-lymphocytes of patients affected by rheumatoid arthritis. Hum Immunol. 2010;71(2):206-211.
112. Lu H, Buchan RJ, Cook SA. MicroRNA-223 regulates Glut4 expression and cardiomyocyte glucose metabolism. Cardiovasc Res. 2010;86(3):410-420.
113. Wang H, Peng W, Ouyang X, Li W, Dai Y. Circulating microRNAs as candidate biomarkers in patients with systemic lupus erythematosus. Transl Res. 2012;160(3):198-206.
114. Pandis I, Ospelt C, Karagianni N, et al. Identification of microRNA-221/222 and microRNA-323-3p association with rheumatoid arthritis via predictions using the human tumour necrosis factor transgenic mouse model. Ann Rheum Dis. 2012;71(10):1716-1723.
115. Lu C, Huang X, Zhang X, et al. miR-221 and miR-155 regulate human dendritic cell development, apoptosis, and IL-12 production through targeting of p27kip1, KPC1, and SOCS-1. Blood. 2011;117(16): 4293-4303.
116. Grigoryev YA, Kurian SM, Hart T, et al. MicroRNA regulation of molecular networks mapped by global microRNA, mRNA, and protein expression in activated T lymphocytes. J Immunol. 2011;187(5): 2233-2243.
117. Liu Y, Chen Q, Song Y, et al. MicroRNA-98 negatively regulates IL-10 production and endotoxin tolerance in macrophages after LPS stimulation. FEBS Lett. 2011;585(12):1963-1968.
118. Hewagama A, Gorelik G, Patel D, et al. Overexpression of X-linked genes in T cells from women with lupus. J Autoimmun. 2013;41:60-71.
119. Verthelyi D. Sex hormones as immunomodulators in health and disease. Int Immunopharmacol. 2001;1(6):983-993.
120. Bouman A, Heineman MJ, Faas MM. Sex hormones and the immune response in humans. Hum Reprod Update. 2005;11(4):411-423.
121. Khan D, Cowan C, Ansar Ahmed S. Estrogen and signaling in the cells of immune system. Adv Neuroimmune Biol. 2012;3(1):73-93.
122. Straub RH. The complex role of estrogens in inflammation. Endocr Rev. 2007;28(5):521-574.
123. Dai R, Phillips RA, Karpuzoglu E, Khan D, Ansar Ahmed S. Estrogen regulates transcription factors STAT-1 and NF-kappaB to promote inducible nitric oxide synthase and inflammatory responses. J Immunol. 2009;183(11):6998-7005.
124. Calippe B, Douin-Echinard V, Laffargue M, et al. Chronic estradiol administration in vivo promotes the proinflammatory response of macrophages to TLR4 activation: involvement of the phosphatidylinositol 3-kinase pathway. J Immunol. 2008;180(12): 7980-7988.
125. Karpuzoglu E, Fenaux JB, Phillips RA, Lengi AJ, Elvinger F, Ansar Ahmed S. Estrogen up-regulates inducible nitric oxide synthase, nitric oxide, and cyclooxygenase-2 in splenocytes activated with T cell stimulants: role of interferon-gamma. Endocrinology. 2006;147(2): 662-671.
126. Ghisletti S, Meda C, Maggi A, Vegeto E. 17beta-estradiol inhibits inflammatory gene expression by controlling NF-kappaB intracellular localization. Mol Cell Biol. 2005;25(8):2957-2968.
127. Yang Z, Wang L. Regulation of microRNA expression and function by nuclear receptor signaling. Cell Biosci. 2011;1(1):31.
128. Paris O, Ferraro L, Grober OM, et al. Direct regulation of microRNA biogenesis and expression by estrogen receptor beta in hormone-responsive breast cancer. Oncogene. 2012;31(38):4196-4206.
129. Klinge CM. Estrogen Regulation of MicroRNA Expression. Curr Genomics. 2009;10(3):169-183.
130. Dai R, Phillips RA, Zhang Y, Khan D, Crasta O, Ansar Ahmed S. Suppression of LPS-induced Interferon-gamma and nitric oxide in splenic lymphocytes by select estrogen-regulated microRNAs: a novel mechanism of immune modulation. Blood. 2008;112(12):4591-4597.
131. Björnström L, Sjöberg M. Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes. Mol Endocrinol. 2005;19(4):833-842.
132. Bhat-Nakshatri P, Wang G, Collins NR, et al. Estradiol-regulated microRNAs control estradiol response in breast cancer cells. Nucleic Acids Res. 2009;37(14):4850-4861.
133. Castellano L, Giamas G, Jacob J, et al. The estrogen receptor-alpha-induced microRNA signature regulates itself and its transcriptional response. Proc Natl Acad Sci U S A. 2009;106(37):15732-15737.
134. Klinge CM. miRNAs and estrogen action. Trends Endocrinol Metab. 2012;23(5):223-233.
135. Di Leva G, Gasparini P, Piovan C, et al. MicroRNA cluster 221-222 and estrogen receptor alpha interactions in breast cancer. J Natl Cancer Inst. 2010;102(10):706-721.
136. Yamagata K, Fujiyama S, Ito S, et al. Maturation of microRNA is hormonally regulated by a nuclear receptor. Mol Cell. 2009;36(2): 340-347.
137. Nothnick WB, Healy C, Hong X. Steroidal regulation of uterine miRNAs is associated with modulation of the miRNA biogenesis components Exportin-5 and Dicer1. Endocrine. 2010;37(2):265-273.
138. Cheng C, Fu X, Alves P, Gerstein M. mRNA expression profiles show differential regulatory effects of microRNAs between estrogen receptor-positive and estrogen receptor-negative breast cancer. Genome Biol. 2009;10(9):R90.
139. Panneerdoss S, Chang YF, Buddavarapu KC, et al. Androgen-responsive microRNAs in mouse Sertoli cells. PLoS One. 2012;7(7): e41146.
140. Coppola V, De Maria R, Bonci D. MicroRNAs and prostate cancer. Endocr Relat Cancer. 2010;17(1):F1-F17.
141. Xu G, Wu J, Zhou L, et al. Characterization of the small RNA transcriptomes of androgen dependent and independent prostate cancer cell line by deep sequencing. PLoS One. 2010;5(11):e15519.
142. Shi XB, Xue L, Yang J, et al. An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells. Proc Natl Acad Sci U S A. 2007;104(50): 19983-19988.
143. Ribas J, Ni X, Haffner M, et al. miR-21: an androgen receptor-regulated microRNA that promotes hormone-dependent and hormone-independent prostate cancer growth. Cancer Res. 2009;69(18): 7165-7169.
144. Mo W, Zhang J, Li X, et al. Identification of novel AR-targeted microRNAs mediating androgen signalling through critical pathways to regulate cell viability in prostate cancer. PLoS One. 2013;8(2): e56592.
145. Fletcher CE, Dart DA, Sita-Lumsden A, Cheng H, Rennie PS, Bevan CL. Androgen-regulated processing of the oncomir miR-27a, which targets Prohibitin in prostate cancer. Hum Mol Genet. 2012;21(14):3112-3127.
146. Delić D, Grosser C, Dkhil M, Al-Quraishy S, Wunderlich F. Testosterone-induced upregulation of miRNAs in the female mouse liver. Steroids. 2010;75(12):998-1004.
147. Palaszynski KM, Loo KK, Ashouri JF, Liu HB, Voskuhl RR. Androgens are protective in experimental autoimmune encephalomyelitis: implications for multiple sclerosis. J Neuroimmunol. 2004;146(1-2):144-152.
148. Roubinian JR, Talal N, Greenspan JS, Goodman JR, Siiteri PK. Delayed androgen treatment prolongs survival in murine lupus. J Clin Invest. 1979;63(5):902-911.
149. Röntzsch A, Thoss K, Petrow PK, Henzgen S, Bräuer R. Amelioration of murine antigen-induced arthritis by dehydroepiandrosterone (DHEA). Inflamm Res. 2004;53(5):189-198.
150. Simon V. Wanted: women in clinical trials. Science. 2005;308(5728): 1517.
151. Arnold AP, Lusis AJ. Understanding the sexome: measuring and reporting sex differences in gene systems. Endocrinology. 2012;153(6):2551-2555.