Top

Published in:

01-12-2016 | Pathogenesis of Type 1 Diabetes (A Pugliese, Section Editor)

MicroRNAs in Type 1 Diabetes: Complex Interregulation of the Immune System, β Cell Function and Viral Infections

Authors: Sonia R. Isaacs, Jie Wang, Ki Wook Kim, Congcong Yin, Li Zhou, Qing Sheng Mi, Maria E. Craig

Published in: Current Diabetes Reports | Issue 12/2016

Abstract

Since the discovery of the first mammalian microRNA (miRNA) more than two decades ago, a plethora of miRNAs has been identified in humans, now amounting to more than 2500. Essential for post-transcriptional regulation of gene networks integral for developmental pathways and immune response, it is not surprising that dysregulation of miRNAs is often associated with the aetiology of complex diseases including cancer, diabetes and autoimmune disorders. Despite massive expansion of small RNA studies and extensive investigation in diverse disease contexts, the role of miRNAs in type 1 diabetes has only recently been explored. Key studies using human islets have recently implicated virus-induced miRNA dysregulation as a pivotal mechanism of β cell destruction, while the interplay between miRNAs, the immune system and β cell survival has been illustrated in studies using animal and cellular models of disease. The role of specific miRNAs as major players in immune system homeostasis highlights their exciting potential as therapeutics and prognostic biomarkers of type 1 diabetes.

Roden M. Diabetes mellitus: definition, classification and diagnosis. Wien Klin Wochenschr. 2016;128 Suppl 2:37–40. doi:10.1007/s00508-015-0931-3.CrossRef

Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG. Analysis of islet inflammation in human type 1 diabetes. Clin Exp Immunol. 2009;155(2):173–81. doi:10.1111/j.1365-2249.2008.03860.x.PubMedPubMedCentralCrossRef

Lehuen A, Diana J, Zaccone P, Cooke A. Immune cell crosstalk in type 1 diabetes. Nat Rev Immunol. 2010;10(7):501–13. doi:10.1038/nri2787.PubMedCrossRef

Uno S, Imagawa A, Okita K, Sayama K, Moriwaki M, Iwahashi H, et al. Macrophages and dendritic cells infiltrating islets with or without beta cells produce tumour necrosis factor-alpha in patients with recent-onset type 1 diabetes. Diabetologia. 2007;50(3):596–601. doi:10.1007/s00125-006-0569-9.PubMedCrossRef

Jun HS, Yoon CS, Zbytnuik L, van Rooijen N, Yoon JW. The role of macrophages in T cell-mediated autoimmune diabetes in nonobese diabetic mice. J Exp Med. 1999;189(2):347–58.PubMedPubMedCentralCrossRef

Tard C, Rouxel O, Lehuen A. Regulatory role of natural killer T cells in diabetes. Biomed J. 2015;38(6):484–95. doi:10.1016/j.bj.2015.04.001.PubMedCrossRef

Galleri L, Sebastiani G, Vendrame F, Grieco FA, Spagnuolo I, Dotta F. Viral infections and diabetes. Adv Exp Med Biol. 2012;771:252–71.PubMed

Pociot F, Akolkar B, Concannon P, Erlich HA, Julier C, Morahan G, et al. Genetics of type 1 diabetes: what’s next? Diabetes. 2010;59(7):1561–71. doi:10.2337/db10-0076.PubMedPubMedCentralCrossRef

Zouidi F, Stayoussef M, Bouzid D, Fourati H, Abida O, Ayed MB, et al. Contribution of PTPN22, CD28, CTLA-4 and ZAP-70 variants to the risk of type 1 diabetes in Tunisians. Gene. 2014;533(1):420–6.PubMedCrossRef

10.

Santin I, Eizirik DL. Candidate genes for type 1 diabetes modulate pancreatic islet inflammation and beta-cell apoptosis. Diabetes Obes Metab. 2013;15 Suppl 3:71–81. doi:10.1111/dom.12162.PubMedCrossRef

11.

Storling J, Brorsson CA. Candidate genes expressed in human islets and their role in the pathogenesis of type 1 diabetes. Curr Diab Rep. 2013;13(5):633–41. doi:10.1007/s11892-013-0408-6.PubMedCrossRef

12.

Winkler C, Krumsiek J, Lempainen J, Achenbach P, Grallert H, Giannopoulou E, et al. A strategy for combining minor genetic susceptibility genes to improve prediction of disease in type 1 diabetes. Genes Immun. 2012;13(7):549–55. doi:10.1038/gene.2012.36.PubMedCrossRef

13.

Oram RA, Patel K, Hill A, Shields B, McDonald TJ, Jones A, et al. A type 1 diabetes genetic risk score can aid discrimination between type 1 and type 2 diabetes in young adults. Diabetes Care. 2016;39(3):337–44. doi:10.2337/dc15-1111.PubMedCrossRef

14.

Hermann R, Knip M, Veijola R, Simell O, Laine AP, Akerblom HK, et al. Temporal changes in the frequencies of HLA genotypes in patients with type 1 diabetes—indication of an increased environmental pressure? Diabetologia. 2003;46(3):420–5. doi:10.1007/s00125-003-1045-4.PubMedCrossRef

15.

Gillespie KM, Bain SC, Barnett AH, Bingley PJ, Christie MR, Gill GV, et al. The rising incidence of childhood type 1 diabetes and reduced contribution of high-risk HLA haplotypes. Lancet. 2004;364(9446):1699–700. doi:10.1016/s0140-6736(04)17357-1.PubMedCrossRef

16.

Fourlanos S, Varney MD, Tait BD, Morahan G, Honeyman MC, Colman PG, et al. The rising incidence of type 1 diabetes is accounted for by cases with lower-risk human leukocyte antigen genotypes. Diabetes Care. 2008;31(8):1546–9. doi:10.2337/dc08-0239.PubMedPubMedCentralCrossRef

17.

Redondo MJ, Jeffrey J, Fain PR, Eisenbarth GS, Orban T. Concordance for islet autoimmunity among monozygotic twins. N Engl J Med. 2008;359(26):2849–50. doi:10.1056/NEJMc0805398.PubMedCrossRef

18.

Hyttinen V, Kaprio J, Kinnunen L, Koskenvuo M, Tuomilehto J. Genetic liability of type 1 diabetes and the onset age among 22,650 young Finnish twin pairs: a nationwide follow-up study. Diabetes. 2003;52(4):1052–5.PubMedCrossRef

19.

Muntoni S, Fonte MT, Stoduto S, Marietti G, Bizzarri C, Crinò A, et al. Incidence of insulin-dependent diabetes mellitus among Sardinian-heritage children born in Lazio region, Italy. Lancet. 1997;349(9046):160–2. doi:10.1016/S0140-6736(96)04241-9.PubMedCrossRef

20.

Kimpimaki T, Kupila A, Hamalainen AM, Kukko M, Kulmala P, Savola K, et al. The first signs of beta-cell autoimmunity appear in infancy in genetically susceptible children from the general population: the Finnish Type 1 Diabetes Prediction and Prevention Study. J Clin Endocrinol Metab. 2001;86(10):4782–8. doi:10.1210/jcem.86.10.7907.PubMed

21.

Gamble DR, Taylor KW. Seasonal incidence of diabetes mellitus. Br Med J. 1969;3(5671):631–3.PubMedPubMedCentralCrossRef

22.

Green A, Patterson CC. Trends in the incidence of childhood-onset diabetes in Europe 1989–1998. Diabetologia. 2001;44 Suppl 3:B3–8.PubMedCrossRef

23.

Oberste MS, Maher K, Kilpatrick DR, Pallansch MA. Molecular evolution of the human enteroviruses: correlation of serotype with VP1 sequence and application to picornavirus classification. J Virol. 1999;73(3):1941–8.PubMedPubMedCentral

24.

Craig ME, Nair S, Stein H, Rawlinson WD. Viruses and type 1 diabetes: a new look at an old story. Pediatr Diabetes. 2013;14(3):149–58. doi:10.1111/pedi.12033.PubMed

25.

Ehrenfeld E, Domingo E, Roos RP. The picornaviruses. Washington, DC: ASM Press; 2010.

26.

Hober D, Sauter P. Pathogenesis of type 1 diabetes mellitus: interplay between enterovirus and host. Nat Rev Endocrinol. 2010;6(5):279–89. doi:10.1038/nrendo.2010.27.PubMedCrossRef

27.

Osipova J, Fischer DC, Dangwal S, Volkmann I, Widera C, Schwarz K, et al. Diabetes-associated microRNAs in pediatric patients with type 1 diabetes mellitus: a cross-sectional cohort study. J Clin Endocrinol Metab. 2014;99(9):E1661–5. doi:10.1210/jc.2013-3868.PubMedCrossRef

28.

Craig ME, Howard NJ, Silink M, Rawlinson WD. Reduced frequency of HLA DRB1*03-DQB1*02 in children with type 1 diabetes associated with enterovirus RNA. J Infect Dis. 2003;187(10):1562–70.PubMedCrossRef

29.

Dotta F, Censini S, van Halteren AG, Marselli L, Masini M, Dionisi S, et al. Coxsackie B4 virus infection of beta cells and natural killer cell insulitis in recent-onset type 1 diabetic patients. Proc Natl Acad Sci U S A. 2007;104(12):5115–20. doi:10.1073/pnas.0700442104.PubMedPubMedCentralCrossRef

30.

• Krogvold L, Edwin B, Buanes T, Frisk G, Skog O, Anagandula M, et al. Detection of a low-grade enteroviral infection in the islets of Langerhans of living patients newly diagnosed with type 1 diabetes. Diabetes. 2015;64(5):1682–7. doi:10.2337/db14-1370. This study successfully isolated enterovirus RNA from four out of six pancreatic samples taken from live patients with T1D using minimal pancreatic tail resection and isolated the enterovirus capsid protein VP1 in all six samples. PubMedCrossRef

31.

Yeung WC, Rawlinson WD, Craig ME. Enterovirus infection and type 1 diabetes mellitus: systematic review and meta-analysis of observational molecular studies. Br Med J. 2011;342:d35. doi:10.1136/bmj.d35.CrossRef

32.

Chehadeh W, Kerr-Conte J, Pattou F, Alm G, Lefebvre J, Wattré P, et al. Persistent infection of human pancreatic islets by coxsackievirus B is associated with alpha interferon synthesis in β cells. J Virol. 2000;74(21):10153–64.PubMedPubMedCentralCrossRef

33.

Nair S. Mechanisms of enterovirus induced β-cells destruction: role of cytokines and signalling pathways [Unpublished doctoral dissertation]: University of New South Wales; 2014.

34.

Oikarinen S, Tauriainen S, Hober D, Lucas B, Vazeou A, Sioofy-Khojine A, et al. Virus antibody survey in different European populations indicates risk association between coxsackievirus B1 and type 1 diabetes. Diabetes. 2014;63(2):655–62. doi:10.2337/db13-0620.PubMedCrossRef

35.

Kang Y, Chatterjee NK, Nodwell MJ, Yoon JW. Complete nucleotide sequence of a strain of coxsackie B4 virus of human origin that induces diabetes in mice and its comparison with nondiabetogenic coxsackie B4 JBV strain. J Med Virol. 1994;44(4):353–61.PubMedCrossRef

36.

Tauriainen S, Oikarinen S, Oikarinen M, Hyoty H. Enteroviruses in the pathogenesis of type 1 diabetes. Semin Immunopathol. 2011;33(1):45–55. doi:10.1007/s00281-010-0207-y.PubMedCrossRef

37.

Richardson SJ, Willcox A, Bone AJ, Foulis AK, Morgan NG. The prevalence of enteroviral capsid protein vp1 immunostaining in pancreatic islets in human type 1 diabetes. Diabetologia. 2009;52(6):1143–51. doi:10.1007/s00125-009-1276-0.PubMedCrossRef

38.

Ambros V. The functions of animal microRNAs. Nature. 2004;431(7006):350–5. doi:10.1038/nature02871.PubMedCrossRef

39.

Huntzinger E, Izaurralde E. Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nat Rev Genet. 2011;12(2):99–110. doi:10.1038/nrg2936.PubMedCrossRef

40.

Sonenberg MRFN. The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat Struct Mol Biol. 2012;19(6):586–93.PubMedCrossRef

41.

Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33.PubMedPubMedCentralCrossRef

42.

Eulalio A, Huntzinger E, Izaurralde E. Getting to the root of miRNA-mediated gene silencing. Cell. 2008;132:9–14.PubMedCrossRef

43.

Wang L, Qin Y, Tong L, Wu S, Wang Q, Jiao Q, et al. MiR-342-5p suppresses coxsackievirus B3 biosynthesis by targeting the 2C-coding region. Antivir Res. 2012;93(2):270–9. doi:10.1016/j.antiviral.2011.12.004.PubMedCrossRef

44.

Chang TC, Mendell JT. microRNAs in vertebrate physiology and human disease. Annu Rev Genomics Hum Genet. 2007;8:215–39.PubMedCrossRef

45.

Lynn FC, Skewes-Cox P, Kosaka Y, McManus MT, Harfe BD, German MS. MicroRNA expression is required for pancreatic islet cell genesis in the mouse. Diabetes. 2007;56(12):2938–45. doi:10.2337/db07-0175.PubMedCrossRef

46.

van de Bunt M, Gaulton KJ, Parts L, Moran I, Johnson PR. The miRNA profile of human pancreatic islets and beta-cells and relationship to type 2 diabetes pathogenesis. PLoS ONE 2013;8.

47.

Joglekar MV, Parekh VS, Mehta S, Bhonde RR, Hardikar AA. MicroRNA profiling of developing and regenerating pancreas reveal post-transcriptional regulation of neurogenin3. Dev Biol. 2007;311:603–12.PubMedCrossRef

48.

Rosero S, Bravo-Egana V, Jiang Z, Khuri S, Tsinoremas N, Klein D, et al. MicroRNA signature of the human developing pancreas. BMC Genomics. 2010;11:509. doi:10.1186/1471-2164-11-509.PubMedPubMedCentralCrossRef

49.

Roggli E, Gattesco S, Caille D, Briet C, Boitard C, Meda P, et al. Changes in microRNA expression contribute to pancreatic beta-cell dysfunction in prediabetic NOD mice. Diabetes. 2012;61(7):1742–51. doi:10.2337/db11-1086.PubMedPubMedCentralCrossRef

50.

Melkman-Zehavi T, Oren R, Kredo-Russo S, Shapira T, Mandelbaum AD, Rivkin N, et al. miRNAs control insulin content in pancreatic beta-cells via downregulation of transcriptional repressors. EMBO J. 2011;30(5):835–45. doi:10.1038/emboj.2010.361.PubMedPubMedCentralCrossRef

51.

van de Bunt M, Gaulton KJ, Parts L, Moran I, Johnson PR, Lindgren CM, et al. The miRNA profile of human pancreatic islets and beta-cells and relationship to type 2 diabetes pathogenesis. PLoS One. 2013;8(1):e55272. doi:10.1371/journal.pone.0055272.PubMedPubMedCentralCrossRef

52.

Klein D, Misawa R, Bravo-Egana V, Vargas N, Rosero S, Piroso J, et al. MicroRNA expression in alpha and beta cells of human pancreatic islets. PLoS One. 2013;8(1):e55064. doi:10.1371/journal.pone.0055064.PubMedPubMedCentralCrossRef

53.

Devasthanam AS, Tomasi TB. Dicer in immune cell development and function. Immunol Investig. 2014;43(2):182–95. doi:10.3109/08820139.2013.863557.CrossRef

54.

Wu J, Shen L, Chen J, Xu H, Mao L. The role of microRNAs in enteroviral infections. The Brazilian Journal of Infectious Diseases. 2015;19(5):510-16. doi:10.1016/j.bjid.2015.06.011.

55.

•• Kim KW, Ho A, Alshabee-Akil A, Hardikar AA, Kay TW, Rawlinson WD, et al. Coxsackievirus B5 infection induces dysregulation of microRNAs predicted to target known type 1 diabetes risk genes in human pancreatic islets. Diabetes. 2016. doi:10.2337/db15-0956. This study was the first to perform global miRNA expression profiling on CVB5-infected human pancreatic islets. It found 33 dysregulated miRNAs in infected cells which were predicted to target 57 out of the 72 known T1D risk genes.

56.

Garo LP, Murugaiyan G. Contribution of microRNAs to autoimmune diseases. Cell Mol Life Sci. 2016;73(10):2041–51. doi:10.1007/s00018-016-2167-4.PubMedCrossRef

57.

Zheng Q, Zhou L, Mi QS. MicroRNA miR-150 is involved in Valpha14 invariant NKT cell development and function. J Immunol. 2012;188(5):2118–26. doi:10.4049/jimmunol.1103342.PubMedCrossRef

58.

Sebastiani G, Grieco FA, Spagnuolo I, Galleri L, Cataldo D, Dotta F. Increased expression of microRNA miR-326 in type 1 diabetic patients with ongoing islet autoimmunity. Diabetes Metab Res Rev. 2011;27(8):862–6. doi:10.1002/dmrr.1262.PubMedCrossRef

59.

Hezova R, Slaby O, Faltejskova P, Mikulkova Z, Buresova I, Raja KR, et al. microRNA-342, microRNA-191 and microRNA-510 are differentially expressed in T regulatory cells of type 1 diabetic patients. Cell Immunol. 2010;260(2):70–4. doi:10.1016/j.cellimm.2009.10.012.PubMedCrossRef

60.

Fornari TA, Donate PB, Assis AF, Macedo C, Sakamoto-Hojo ET, Donadi EA, et al. Comprehensive survey of miRNA-mRNA interactions reveals that Ccr7 and Cd247 (CD3 zeta) are posttranscriptionally controlled in pancreas infiltrating T Lymphocytes of non-obese diabetic (NOD) mice. PLoS One. 2015;10(11):e0142688. doi:10.1371/journal.pone.0142688.PubMedPubMedCentralCrossRef

61.

Baroukh N, Ravier MA, Loder MK, Hill EV, Bounacer A, Scharfmann R, et al. MicroRNA-124a regulates Foxa2 expression and intracellular signaling in pancreatic beta-cell lines. J Biol Chem. 2007;282(27):19575–88. doi:10.1074/jbc.M611841200.PubMedCrossRef

62.

63.

Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, et al. A pancreatic islet-specific microRNA regulates insulin secretion. Nature. 2004;432(7014):226–30. doi:10.1038/nature03076.PubMedCrossRef

64.

Lahmy R, Soleimani M, Sanati MH, Behmanesh M, Kouhkan F, Mobarra N. MiRNA-375 promotes beta pancreatic differentiation in human induced pluripotent stem (hiPS) cells. Mol Biol Rep. 2014;41(4):2055–66. doi:10.1007/s11033-014-3054-4.PubMedCrossRef

65.

Kloosterman WP, Lagendijk AK, Ketting RF, Moulton JD, Plasterk RH. Targeted inhibition of miRNA maturation with morpholinos reveals a role for miR-375 in pancreatic islet development. PLoS Biol. 2007;5(8):e203. doi:10.1371/journal.pbio.0050203.PubMedPubMedCentralCrossRef

66.

Bao L, Fu X, Si M, Wang Y, Ma R, Ren X, et al. MicroRNA-185 targets SOCS3 to inhibit beta-cell dysfunction in diabetes. PLoS One. 2015;10(2):e0116067. doi:10.1371/journal.pone.0116067.PubMedPubMedCentralCrossRef

67.

Bravo-Egana V, Rosero S, Molano RD, Pileggi A, Ricordi C, Dominguez-Bendala J, et al. Quantitative differential expression analysis reveals miR-7 as major islet microRNA. Biochem Biophys Res Commun. 2008;366(4):922–6. doi:10.1016/j.bbrc.2007.12.052.PubMedCrossRef

68.

Joglekar MV, Joglekar VM, Hardikar AA. Expression of islet-specific microRNAs during human pancreatic development. Gene Expr Patterns. 2009;9(2):109–13. doi:10.1016/j.gep.2008.10.001.PubMedCrossRef

69.

Correa-Medina M, Bravo-Egana V, Rosero S, Ricordi C, Edlund H, Diez J, et al. MicroRNA miR-7 is preferentially expressed in endocrine cells of the developing and adult human pancreas. Gene Expr Patterns. 2009;9(4):193–9. doi:10.1016/j.gep.2008.12.003.PubMedCrossRef

70.

Bushati N, Cohen SM. microRNA functions. Annu Rev Cell Dev Biol. 2007;23:175–205. doi:10.1146/annurev.cellbio.23.090506.123406.PubMedCrossRef

71.

Roggli E, Britan A, Gattesco S, Lin-Marq N, Abderrahmani A, Meda P, et al. Involvement of microRNAs in the cytotoxic effects exerted by proinflammatory cytokines on pancreatic beta-cells. Diabetes. 2010;59(4):978–86. doi:10.2337/db09-0881.PubMedPubMedCentralCrossRef

72.

Ruan Q, Wang T, Kameswaran V, Wei Q, Johnson DS, Matschinsky F, et al. The microRNA-21-PDCD4 axis prevents type 1 diabetes by blocking pancreatic beta cell death. Proc Natl Acad Sci U S A. 2011;108(29):12030–5. doi:10.1073/pnas.1101450108.PubMedPubMedCentralCrossRef

73.

Lovis P, Gattesco S, Regazzi R. Regulation of the expression of components of the exocytotic machinery of insulin-secreting cells by microRNAs. Biol Chem. 2008;389(3):305–12. doi:10.1515/bc.2008.026.PubMedCrossRef

74.

Lovis P, Roggli E, Laybutt DR, Gattesco S, Yang JY, Widmann C, et al. Alterations in microRNA expression contribute to fatty acid-induced pancreatic beta-cell dysfunction. Diabetes. 2008;57(10):2728–36. doi:10.2337/db07-1252.PubMedPubMedCentralCrossRef

75.

Plaisance V, Abderrahmani A, Perret-Menoud V, Jacquemin P, Lemaigre F, Regazzi R. MicroRNA-9 controls the expression of Granuphilin/Slp4 and the secretory response of insulin-producing cells. J Biol Chem. 2006;281(37):26932–42. doi:10.1074/jbc.M601225200.PubMedCrossRef

76.

Tang X, Muniappan L, Tang G, Ozcan S. Identification of glucose-regulated miRNAs from pancreatic {beta} cells reveals a role for miR-30d in insulin transcription. RNA. 2009;15(2):287–93. doi:10.1261/rna.1211209.PubMedPubMedCentralCrossRef

77.

Trajkovski M, Hausser J, Soutschek J, Bhat B, Akin A, Zavolan M, et al. MicroRNAs 103 and 107 regulate insulin sensitivity. Nature. 2011;474(7353):649–53. doi:10.1038/nature10112.PubMedCrossRef

78.

Hennessy E, Clynes M, Jeppesen PB, O’Driscoll L. Identification of microRNAs with a role in glucose stimulated insulin secretion by expression profiling of MIN6 cells. Biochem Biophys Res Commun. 2010;396(2):457–62. doi:10.1016/j.bbrc.2010.04.116.PubMedCrossRef

79.

Gerin I, Clerbaux LA, Haumont O, Lanthier N, Das AK, Burant CF, et al. Expression of miR-33 from an SREBP2 intron inhibits cholesterol export and fatty acid oxidation. J Biol Chem. 2010;285(44):33652–61. doi:10.1074/jbc.M110.152090.PubMedPubMedCentralCrossRef

80.

Musso G, Gambino R, Cassader M. Emerging molecular targets for the treatment of nonalcoholic fatty liver disease. Annu Rev Med. 2010;61:375–92. doi:10.1146/annurev.med.60.101107.134820.PubMedCrossRef

81.

Feng B, Cao Y, Chen S, Ruiz M, Chakrabarti S. miRNA-1 regulates endothelin-1 in diabetes. Life Sci. 2014;98(1):18–23. doi:10.1016/j.lfs.2013.12.199.PubMedCrossRef

82.

Nielsen LB, Wang C, Sorensen K, Bang-Berthelsen CH, Hansen L, Andersen ML, et al. Circulating levels of microRNA from children with newly diagnosed type 1 diabetes and healthy controls: evidence that miR-25 associates to residual beta-cell function and glycaemic control during disease progression. Exp Diabetes Res. 2012;2012:896362. doi:10.1155/2012/896362.PubMedPubMedCentral

83.

Shi Z, Zhao C, Guo X, Ding H, Cui Y, Shen R, et al. Differential expression of microRNAs in omental adipose tissue from gestational diabetes mellitus subjects reveals miR-222 as a regulator of ERalpha expression in estrogen-induced insulin resistance. Endocrinology. 2014;155(5):1982–90. doi:10.1210/en.2013-2046.PubMedCrossRef

84.

Bernstein E, Caudy AA, Hammond SM, Hannon GJ. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001;409(6818):363–6. doi:10.1038/35053110.PubMedCrossRef

85.

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(9):1367–73. doi:10.1084/jem.20050572.PubMedPubMedCentralCrossRef

86.

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):261–9. doi:10.1084/jem.20050678.PubMedPubMedCentralCrossRef

87.

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(5):860–74. doi:10.1016/j.cell.2008.02.020.PubMedCrossRef

88.

Murugaiyan G, Beynon V, Mittal A, Joller N, Weiner HL. Silencing microRNA-155 ameliorates experimental autoimmune encephalomyelitis. J Immunol. 2011;187(5):2213–21. doi:10.4049/jimmunol.1003952.PubMedPubMedCentralCrossRef

89.

O’Connell RM, Kahn D, Gibson WS, Round JL, Scholz RL, Chaudhuri AA, et al. MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity. 2010;33(4):607–19. doi:10.1016/j.immuni.2010.09.009.PubMedPubMedCentralCrossRef

90.

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. 2010;142(6):914–29. doi:10.1016/j.cell.2010.08.012.PubMedPubMedCentralCrossRef

91.

Liu YL, Wu W, Xue Y, Gao M, Yan Y, Kong Q, et al. MicroRNA-21 and -146b are involved in the pathogenesis of murine viral myocarditis by regulating TH-17 differentiation. Arch Virol. 2013;158(9):1953–63. doi:10.1007/s00705-013-1695-6.PubMedCrossRef

92.

Murugaiyan G, Garo LP, Weiner HL. MicroRNA-21, T helper lineage and autoimmunity. Oncotarget. 2015;6(12):9644–5. doi:10.18632/oncotarget.3928.PubMedPubMedCentralCrossRef

93.

Morita S, Hara A, Kojima I, Horii T, Kimura M, Kitamura T, et al. Dicer is required for maintaining adult pancreas. PLoS One. 2009;4(1):e4212. doi:10.1371/journal.pone.0004212.PubMedPubMedCentralCrossRef

94.

Latreille M, Hausser J, Stutzer I, Zhang Q, Hastoy B, Gargani S, et al. MicroRNA-7a regulates pancreatic beta cell function. J Clin Invest. 2014;124(6):2722–35. doi:10.1172/JCI73066.PubMedPubMedCentralCrossRef

95.

Wang Y, Liu J, Liu C, Naji A, Stoffers DA. MicroRNA-7 regulates the mTOR pathway and proliferation in adult pancreatic beta-cells. Diabetes. 2013;62(3):887–95. doi:10.2337/db12-0451.PubMedPubMedCentralCrossRef

96.

Filios SR, Xu G, Chen J, Hong K, Jing G, Shalev A. MicroRNA-200 is induced by thioredoxin-interacting protein and regulates Zeb1 protein signaling and beta cell apoptosis. J Biol Chem. 2014;289(52):36275–83. doi:10.1074/jbc.M114.592360.PubMedPubMedCentralCrossRef

97.

Gennari SP, Mirkovic J, Macdonald MC. Animacy and competition in relative clause production: a cross-linguistic investigation. Cogn Psychol. 2012;65(2):141–76. doi:10.1016/j.cogpsych.2012.03.002.PubMedPubMedCentralCrossRef

98.

Yin C, Weiland M, Miao ZM, Li C, Zhou L, Mi QS. Deletion of microRNA miR-146a does not prevent streptozotocin-induced murine autoimmune type 1 diabetes. Diab Metab. 2016. doi:10.1016/j.diabet.2016.03.007.

99.

Guay C, Regazzi R. Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol. 2013;9(9):513–21. doi:10.1038/nrendo.2013.86.PubMedCrossRef

100.

Qi J, Wang J, Katayama H, Sen S, Liu SM. Circulating microRNAs (cmiRNAs) as novel potential biomarkers for hepatocellular carcinoma. Neoplasma. 2013;60(2):135–42.PubMedPubMedCentralCrossRef

101.

Ji J, Wang XW. New kids on the block: diagnostic and prognostic microRNAs in hepatocellular carcinoma. Cancer Biol Ther. 2009;8(18):1686–93.PubMedCrossRef

102.

Zen K, Zhang CY. Circulating microRNAs: a novel class of biomarkers to diagnose and monitor human cancers. Med Res Rev. 2012;32(2):326–48. doi:10.1002/med.20215.PubMedCrossRef

103.

Zhu W, Qin W, Atasoy U, Sauter ER. Circulating microRNAs in breast cancer and healthy subjects. BMC Res Notes. 2009;2:89. doi:10.1186/1756-0500-2-89.PubMedPubMedCentralCrossRef

104.

Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105(30):10513–8. doi:10.1073/pnas.0804549105.PubMedPubMedCentralCrossRef

105.

Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18(10):997–1006. doi:10.1038/cr.2008.282.PubMedCrossRef

106.

Sebastiani G. MicroRNA expression fingerprint in serum of type 1 diabetic patients. Diabetologia 2012;55(s48).

107.

El Ouaamari A, Baroukh N, Martens GA, Lebrun P, Pipeleers D, van Obberghen E. miR-375 targets 3′-phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic beta-cells. Diabetes. 2008;57(10):2708–17. doi:10.2337/db07-1614.PubMedPubMedCentralCrossRef

108.

Farr RJ, Joglekar MV, Taylor CJ, Hardikar AA. Circulating non-coding RNAs as biomarkers of beta cell death in diabetes. Pediatr Endocrinol Rev. 2013;11(1):14–20.PubMed

109.

Erener S, Mojibian M, Fox JK, Denroche HC, Kieffer TJ. Circulating miR-375 as a biomarker of beta-cell death and diabetes in mice. Endocrinology. 2013;154(2):603–8. doi:10.1210/en.2012-1744.PubMedCrossRef

110.

Seyhan AA, Nunez Lopez YO, Xie H, Yi F, Mathews C, Pasarica M, et al. Pancreas-enriched miRNAs are altered in the circulation of subjects with diabetes: a pilot cross-sectional study. Sci Rep. 2016;6:31479. doi:10.1038/srep31479.PubMedPubMedCentralCrossRef

111.

Sullivan CS, Ganem D. MicroRNAs and viral infection. Mol Cell. 2005;20(1):3–7. doi:10.1016/j.molcel.2005.09.012.PubMedCrossRef

112.

Berkhout B, Jeang KT. RISCy business: microRNAs, pathogenesis, and viruses. J Biol Chem. 2007;282(37):26641–5. doi:10.1074/jbc.R700023200.PubMedCrossRef

113.

Cai X, Lu S, Zhang Z, Gonzalez CM, Damania B, Cullen BR. Kaposi’s sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells. Proc Natl Acad Sci U S A. 2005;102(15):5570–5. doi:10.1073/pnas.0408192102.PubMedPubMedCentralCrossRef

114.

Li Z, Cui X, Li F, Li P, Ni M, Wang S, et al. Exploring the role of human miRNAs in virus-host interactions using systematic overlap analysis. Bioinformatics. 2013;29(19):2375–9. doi:10.1093/bioinformatics/btt391.PubMedCrossRef

115.

Ho BC, Yang PC, Yu SL. MicroRNA and pathogenesis of enterovirus infection. Viruses. 2016;8(1):e11. doi:10.3390/v8010011.PubMedCrossRef

116.

Zheng Z, Ke X, Wang M, He S, Li Q, Zheng C, et al. Human microRNA hsa-miR-296-5p suppresses enterovirus 71 replication by targeting the viral genome. J Virol. 2013;87(10):5645–56. doi:10.1128/JVI.02655-12.PubMedPubMedCentralCrossRef

117.

Wen BP, Dai HJ, Yang YH, Zhuang Y, Sheng R. MicroRNA-23b inhibits enterovirus 71 replication through downregulation of EV71 VPl protein. Intervirology. 2013;56(3):195–200. doi:10.1159/000348504.PubMedCrossRef

118.

Yang Z, Tien P. MiR373 and miR542-5p regulate the replication of enterovirus 71 in rhabdomyosarcoma cells. Sheng wu gong cheng xue bao = Chin J Biotechnol. 2014;30(6):943–53.

119.

Tong L, Lin L, Wu S, Guo Z, Wang T, Qin Y, et al. MiR-10a* up-regulates coxsackievirus B3 biosynthesis by targeting the 3D-coding sequence. Nucleic Acids Res. 2013;41(6):3760–71. doi:10.1093/nar/gkt058.PubMedPubMedCentralCrossRef

120.

Ho BC, Yu SL, Chen JJ, Chang SY, Yan BS, Hong QS, et al. Enterovirus-induced miR-141 contributes to shutoff of host protein translation by targeting the translation initiation factor eIF4E. Cell Host Microbe. 2011;9(1):58–69. doi:10.1016/j.chom.2010.12.001.PubMedCrossRef

121.

Lui YL, Tan TL, Woo WH, Timms P, Hafner LM, Tan KH, et al. Enterovirus71 (EV71) utilise host microRNAs to mediate host immune system enhancing survival during infection. PLoS One. 2014;9(7):e102997. doi:10.1371/journal.pone.0102997.PubMedPubMedCentralCrossRef

122.

Ho BC, Yu IS, Lu LF, Rudensky A, Chen HY, Tsai CW, et al. Inhibition of miR-146a prevents enterovirus-induced death by restoring the production of type I interferon. Nat Commun. 2014;5:3344. doi:10.1038/ncomms4344.PubMed

123.

Zhang Q, Xiao Z, He F, Zou J, Wu S, Liu Z. MicroRNAs regulate the pathogenesis of CVB3-induced viral myocarditis. Intervirology. 2013;56(2):104–13. doi:10.1159/000343750.PubMedCrossRef

124.

Wang RY, Weng KF, Huang YC, Chen CJ. Elevated expression of circulating miR876-5p is a specific response to severe EV71 infections. Sci Rep. 2016;6:24149. doi:10.1038/srep24149.PubMedPubMedCentralCrossRef

125.

Hemida MG, Ye X, Zhang HM, Hanson PJ, Liu Z, McManus BM, et al. MicroRNA-203 enhances coxsackievirus B3 replication through targeting zinc finger protein-148. Cell Mol Life Sci. 2013;70(2):277–91. doi:10.1007/s00018-012-1104-4.PubMedCrossRef

126.

Filios SR, Shalev A. Beta-cell microRNAs: small but powerful. Diabetes. 2015;64(11):3631–44. doi:10.2337/db15-0831.PubMedPubMedCentralCrossRef

127.

Shaer A, Azarpira N, Karimi MH, Soleimani M, Dehghan S. Differentiation of human-induced pluripotent stem cells into insulin-producing clusters by MicroRNA-7. Exp Clin Transplant. 2015. doi:10.6002/ect.2014.0144.PubMed

128.

Yang CS, Li Z, Rana TM. microRNAs modulate iPS cell generation. RNA. 2011;17(8):1451–60. doi:10.1261/rna.2664111.PubMedPubMedCentralCrossRef

129.

Pileggi A, Klein D, Fotino C, Bravo-Egana V, Rosero S, Doni M, et al. MicroRNAs in islet immunobiology and transplantation. Immunol Res. 2013;57(1–3):185–96. doi:10.1007/s12026-013-8436-5.PubMedCrossRef

Title: MicroRNAs in Type 1 Diabetes: Complex Interregulation of the Immune System, β Cell Function and Viral Infections
Authors: Sonia R. Isaacs
Jie Wang
Ki Wook Kim
Congcong Yin
Li Zhou
Qing Sheng Mi
Maria E. Craig
Publication date: 01-12-2016
Publisher: Springer US
Published in: Current Diabetes Reports / Issue 12/2016
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI: https://doi.org/10.1007/s11892-016-0819-2

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

MicroRNAs in Type 1 Diabetes: Complex Interregulation of the Immune System, β Cell Function and Viral Infections

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 12/2016

Clinical Components of Telemedicine Programs for Diabetic Retinopathy

Urogenital Autonomic Dysfunction in Diabetes

Redesigning Diabetes Care: Defining the Role of Endocrinologists Among Alternative Providers

Biomarkers of Diabetic Retinopathy

Targeting Tie2 for Treatment of Diabetic Retinopathy and Diabetic Macular Edema

Using Group Medical Visits With Those Who Have Diabetes: Examining the Evidence

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page