Immune Netw.  2011 Dec;11(6):309-323. 10.4110/in.2011.11.6.309.

MicroRNAs in Human Diseases: From Lung, Liver and Kidney Diseases to Infectious Disease, Sickle Cell Disease and Endometrium Disease

• Ha TY

• KMID: 2150715
• DOI: http://doi.org/10.4110/in.2011.11.6.309

Abstract

MicroRNAs (miRNAs) are a class of naturally occurring small non-coding RNAs of about 22 nucleotides that have recently emerged as important regulators of gene expression at the posttranscriptional level. Recent studies provided clear evidence that microRNAs are abundant in the lung, liver and kidney and modulate a diverse spectrum of their functions. Moreover, a large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as infectious diseases, sickle cell disease and endometrium diseases as well as lung, liver and kidney diseases. As a consequence of extensive participation of miRNAs in normal functions, alteration and/or abnormalities in miRNAs should have importance in human diseases. Beside their important roles in patterning and development, miRNAs also orchestrated responses to pathogen infections. Particularly, emerging evidence indicates that viruses use their own miRNAs to manipulate both cellular and viral gene expression. Furthermore, viral infection can exert a profound impact on the host cellular miRNA expression profile, and several RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Here I briefly summarize the newly discovered roles of miRNAs in various human diseases including infectious diseases, sickle cell disease and enodmetrium diseases as well as lung, liver and kidney diseases.

Keyword

MicroRNAs; Lung; Liver; Kidney; Infectious diseases; Sickle cell disease

MeSH Terms

Anemia, Sickle Cell
Communicable Diseases
Endometrium
Female
Gene Expression
Genes, Viral
Homeostasis
Humans
Kidney
Kidney Diseases
Liver
Lung
MicroRNAs
Nucleotides
RNA Viruses
RNA, Small Untranslated
MicroRNAs
Nucleotides
RNA, Small Untranslated

Figure

• 

  Figure 1 miRNAs involving in pathogenic processes in lung. There is evidence that up-regulation or down-regulation of miRNAs is critical for the lung development and homeostasis and thus may contribute to development of pathological pulmonary conditions, including lung carcinogenesis, idiopathic pulmonary fibrosis, cystic fibrosis, chroinic obstructive pulmonary disease, smoking-related diseases and pulmonary allergy and asthma (For the details, see Text).

• 

  Figure 2 Possible functions of viral miRNAs. Many viruses have been found to encode miRNAs that regulate both viral and host mRNA. miRNAs encoded in the viral genome have the potential to reshape the cellular environment to maximize viral replication. miRNAs could contribute to the maintenance and/or establishment of viral latent infection by protecting infected cells from undergoing apoptosis. miRNAs probably interfere with the host immune response, including antigen presentation and the IFN system. Viral miRNAS can suppress host cell gene involved in antiviral immunity and can control cell growth. IFN-β production ("cytokine storm") can induce and/or modulate expression of numerous cellular miRNAs. Cellular miRNAs influence the replication of virus and antiviral activity may be mediated by IFN through cellular miRNAs.

Reference

1. Tili E, Michaille JJ, Calin GA. Expression and function of micro-RNAs in immune cells during normal or disease state. Int J Med Sci. 2008. 5:73–79.

2. Slaby O, Svoboda M, Michalek J, Vyzula R. MicroRNAs in colorectal cancer: translation of molecular biology into clinical application. Mol Cancer. 2009. 8:102.

3. Small EM, Olson EN. Pervasive roles of microRNAs in cardiovascular biology. Nature. 2011. 469:336–342.

4. Ha TY. MicroRNAs in human diseases: from cancer to cardiovascular disease. Immune Netw. 2011. 11:135–154.

5. Ha TY. MicroRNAs in human diseases: from autoimmune diseases to skin, psychiatric and neurodegenerative diseases. Immune Netw. 2011. 11:227–244.

6. Ha TY. The role of microRNAs in regulatory T cells and in the immune response. Immune Netw. 2011. 11:11–41.

7. 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.

8. Wang GK, Zhu JQ, Zhang JT, Li Q, Li Y, He J, Qin YW, Jing Q. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J. 2010. 31:659–666.

9. Miller BH, Wahlestedt C. MicroRNA dysregulation in psychiatric disease. Brain Res. 2010. 1338:89–99.

10. Belver L, de Yébenes VG, Ramiro AR. MicroRNAs prevent the generation of autoreactive antibodies. Immunity. 2010. 33:713–722.

11. Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010. 466:835–840.

12. Perera RJ, Ray A. MicroRNAs in the search for understanding human diseases. BioDrugs. 2007. 21:97–104.

13. Dai R, Ahmed SA. MicroRNA, a new paradigm for understanding immunoregulation, inflammation, and autoimmune diseases. Transl Res. 2011. 157:163–179.

14. Lu M, Zhang Q, Deng M, Miao J, Guo Y, Gao W, Cui Q. An analysis of human microRNA and disease associations. PLoS One. 2008. 3:e3420.

15. Tomankova T, Petrek M, Kriegova E. Involvement of microRNAs in physiological and pathological process in the lung. Respir Res. 2010. 11:159.

16. Pottelberge GR, Mestadgh P, Bracke KR, Thas GF, Van Dume YMTA, Joos GF, Vandesompele J, Brusselle GG. MicroRNA expression in induced sputum of smokers and patients with chronic obstructive pulmonary diseases. Am J Respir Crit Care Med. 2011. 183:898–906.

17. Caramori G, Casolari P, Cavallesco GN, Giuffre S, Adeock I, Papi A. Mechanisms involved in lung cancer development in COPD. Int J Biochem Cell Biol. 2011. 43:1030–1044.

18. Jopling CI, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA. Science. 2005. 309:1577–1581.

19. Chen XM. MicroRNA signatures in liver diseases. World J Gastroenterol. 2009. 15:1665–1672.

20. Trang P, Weidhaas JB, Slack FJ. MicroRNAs as potential cancer therapeutics. Oncogene. 2008. 27:S52–S57.

21. Li LM, Hou DX, Guo YL, Yang JW, Liu Y, Zhang CY, Zen K. Role of microRNA-214-targeting phosphatase and tensin homolog in advanced glycation end product-induced apoptosis delay in monocytes. J Immunol. 2011. 186:2552–2560.

22. Lu LF, Liston A. MicroRNA in the immune system, microRNA as an immune system. Immunology. 2009. 127:291–298.

23. Li Y, Chan EY, Li J, Ni C, Peng X, Rosenzweig E, Tumpey TM, Katz MG. MicroRNA expression and virulence in pandemic influenza virus-infected mice. J Virol. 2010. 84:3023–3032.

24. Cullen BR. Viruses and microRNAs. Nat Genet. 2006. 38:S25–S30.

25. Pallante P, Visone R, Croce CM, Fusco A. Deregulation of microRNA expression in follicular cell-derived human thyroid carcinomas. Endocrine-Related Cancer. 2010. 17:F91–F104.

26. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006. 6:857–866.

27. Shenouda SK, Alahari SK. MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev. 2009. 28:369–378.

28. Bartel DP. MicroRNAs: Genomics, biogenesis, mechanisms, and funtion. Cell. 2004. 116:281–297.

29. Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 2009. 10:126–139.

30. Kim VN. Small RNAs: Classification, biogenesis, and function. Mol Cells. 2005. 19:1–15.

31. Boyd SD. Everything you wanted to know about small RNA but were afraid to ask. Lab Invest. 2008. 88:569–578.

32. Rodriguez A, Crffiths-Jones S, Ashurst JL, Bradely A. Identification of mammalian microRNA host genes and transcription units. Genome Res. 2004. 14:1902–1910.

33. Sonkoly E, Pivarcsi A. Advances in microRNAs: implications for immunity and inflammatory diseases. J Cell Mol Med. 2009. 13:24–38.

34. Hunsberger JG, Austin DR, Chen G, Manji HK. MicroRNAs in mental health: from biological underpinnings to potential therapies. Neuromolecular Med. 2009. 11:173–182.

35. Sato T, Liu X, Melson A, Nakanishi M, Kanaji N, Wang X, Kim M, Li Y, Sun J, Michalski J, Patil A, Basma H, Holz O, Magnussen H, Rennard SI. Reduced miR-146a increases prostaglandin E2 in chronic obstructive pulmonary disease fibroblast. Am J Respir Crit Care Med. 2010. 182:1020–1029.

36. Schembri F, Sridhar S, Perdomo C, Gustafson AM, Zhang X, Ergun A, Lu J, Liu G, Zhang X, Bowers J, Vaziri C, Ott K, Sensinger K, Collins JJ, Brody JS, Getts R, Lenburg ME, Spira A. MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium. Proc Natl Acad Sci U S A. 2009. 106:2319–2324.

37. Pandit KV, Corcoran D, Yousef H, Yarlagadda M, Tzouvelekis A, Gibson KF, Konishi K, Yousem SA, Singh M, Handley D, Richards T, Selman M, Watkins SC, Pardo A, Ben-Yehudah A, Bouros D, Eickelberg O, Ray P, Benos PV, Kaminski N. Inhibition and role of let-7d in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2010. 182:220–229.

38. Liu G, Frigger A, Yang Y, Milosevic J, Ding Q, Thannickal VJ, Kaminiski N, Abraham E. miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis. J Exp Med. 2010. 207:1589–1597.

39. Coward WR, Saini G, Jenkins G. The pathogenesis of idiopathic pulmonary fibrosis. Ther Adv Respir Dis. 2010. 4:367–388.

40. Oglesby IK, Bray IM, Chotirmall SH, Stallings RL, O'Neill SJ, McElvaney NG, Greene CM. miR-126 is downregulated in cystic fibrosis airway epitherlial cells and regualtes TOM1 expression. J Immunol. 2010. 184:1702–1709.

41. Miranda RC, Pietrzykowski AZ, Tang Y, Sathyan P, Mayfield D, Keshavarzian A, Sampson W, Hereld D. MicroRNAs: Master regulators of ethanol abuse and toxicity? Alcohol Clin Exp Res. 2010. 34:575–587.

42. Tang Y, Banan A, Forsyth CB, Fields JZ, Lau CK, Zhang LJ, Keshavarzian A. Effect of alcohol on miR-212 expression in intestinal epithelial cells and its potential role in alcoholic liver disease. Alcohol Clin Exp Res. 2008. 32:355–364.

43. Otto EA, Trapp ML, Schulthesis UT, Helou J. NEK8 mutations affect ciliary and centrosomal localization and may cause nepronophthisis. J Am Soc Nephrol. 2008. 19:587–592.

44. Pandey P, Brors B, Srivastava PK, Bott A, Boehn SNE, Groene HJ, Gretz N. Microarray-based approach identifies microRNAs and their target functional patterns in polycystic kidney disease. BMC Genomics. 2008. 9:624.

45. Sarnow P, Jopling CL, Norman KL, Schutz S, Wehner KA. MicroRNAs: expression, avoidance and subversion by vertebrate viruses. Nat Rev Microbiol. 2006. 4:651–659.

46. Xiao B, Liu Z, Li BS, Tang B, Li W, Guo G, Shi Y, Wang F, Wu Y, Tong WD, Guo H, Mao XH, Zou QM. Induction of microRNA-155 during Helicobacter pylori infection and its negative regulatory role in the inflammatory response. J Infect Dis. 2009. 200:916–925.

47. Gupta A, Gartner JJ, Sethupathy P, Hatzigeorgiou AG, Fraser NW. Anti-apoptotic function of a microRNA encoded by the HSV-1 latency-associated transcript. Nature. 2006. 442:82–85.

48. Stern-Ginossar N, Elefant N, Zimmermann A, Wolf DG, Saleh N, Biton M, Horwitz E, Prokocimer Z, Prichard M, Hahn G, Goldman-Wohl D, Greenfield C, Yagel S, Hengel H, Altuvia Y, Margalit H, Mandelboim O. Host immune system gene targeting by a viral miRNA. Science. 2007. 317:376–381.

49. Song L, Liu H, Gao S, Jiang W, Huang W. Cellular microRNAS inhibit replication of the H1N1 influenza A virus in infected cells. J Virol. 2010. 84:8849–8860.

50. Guo W, Li JT, Pan X, Wei L, Wu JY. Candidate Mycobacterium tuberculosis genes targeted by human microRNAs. Protein Cell. 2010. 1:419–421.

51. Liu Y, Wang X, Jiang J, Cao Z, Yang B, Cheng X. Modulation of T cell cytokine production by miR-144^* with elevated expression in patients with pulmonary tuberculosis. Mol Immunol. 2011. 48:1084–1090.

52. De Flora S, Bonanni P. The prevention of infection-associated cancers. Carcinogenesis. 2011. 32:787–795.

53. Schulte LN, Eulalio A, Mollenkopf HJ, Reinhardt R, Vogel J. Analysis of the host microRNA response to Salmonella uncovers the control of major cytokines by the let-7 family. EMBO J. 2011. 30:1977–1989.

54. Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, Fabbri M, Alder H, Liu CG, Calin GA, Croce CM. 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. 179:5082–5089.

55. Orkin SH, Higgs DR. Sickle cell disease at 100 years. Science. 2010. 329:291–292.

56. Chen SY, Wang Y, Telen MJ, Chi JT. The genomic analysis of erythrocyte microRNA expression in sickle cell disease. PLoS ONE. 2008. 3:e2360.

57. Sankaran VG, Menne TF, Scepanovic D, Vergillo JA, Ji P, Kim J, Thiru P, Orkin SH, Lander ES, Lodish HF. MicroRNA-15a and -16-1 act via MYB to elevate fetal hemoglobin expression in human trisomy 13. Proc Natl Acad Sci. 2011. 108:1519–1524.

58. Pan Q, Chegini N. MicroRNA signature and regulatory functions in the endometrium during normal and disease states. Semin Reprod Med. 2008. 26:479–493.

59. Germain RN, Meier-Schellersheim M, Nita-Lazar A, Fraser I. Systems biology in immunology: A computational modeling perspective. Annu Rev Immunol. 2011. 29:527–585.

60. Izzotti A, Calin GA, Arrigo P, Steele VE, Croce CM, De Flora S. Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke. FASEB J. 2009. 23:806–812.

61. Liu X, Wang T, Wakita T, Yang W. Systematic identification of microRNA and messenger RNA profiles in hepatitis C virus-infected human hepatoma cells. Virology. 2010. 398:57–67.

62. Kota J, Chivukula RR, O'Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, Chang TC, Vivekanandan P, Torbenson M, Clark KR, Mendell JR, Mendell JT. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell. 2009. 137:1005–1017.

63. Bala S, Marcos M, Szabo G. Emerging role of microRNAs in liver diseases. World J Gastroenterol. 2009. 15:5633–5640.

64. Hildebrandt F, Zhou W. Nephronophthisis-associated ciliopathies. J Am Soc Nephrol. 2007. 18:1855–1871.

65. Witwer KW, Sisk JM, Gama L, Clements JE. MicroRNA regulation of IFN-β protein expression: Rapid and sensitive modulation of the innate immune response. J Immunol. 2010. 184:2369–2376.

66. Belair C, Darfeuille F, Staedel C. Helicobacter pylori and gastric cancer: possible role of microRNA in this intimate relationship. Clin Microbiol Infect. 2009. 15:806–812.

67. Zhang GL, Li YX, Zheng SQ, Liu M, Li X, Tang H. Suppression of hepatitis B virus replication by microRNA-199a-3p and microRNA-210. Antiviral Res. 2010. 88:169–173.

68. Ura S, Honda M, Yamashita T, Ueda T, Takatori H, Nishino R, Sunakozaka H, Sakai Y, Horimoto K, Kaneko S. Differential microRNA expression between hepatitis B and hepatitis C leading disease progression to hepatocellular carcinoma. Hepatology. 2009. 49:1098–1112.

69. Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, Chisari FV, David M. Interferon modulation of cellular microRNs as an antiviral mechanism. Nature. 2007. 449:919–922.

70. Ohlsson Teague EM, Vand er Hoek KH, Vand er Hoek MB, Perry N, Wagaarachchi P, Robertson SA, Print CG, Hull LM. MicroRNA-regulated pathways associated with endometriosis. Mol Endocrinol. 2009. 23:265–275.

71. Davidson MR, Larsen JE, Yang IA, Hayward NK, Clarke BE, Duhig EE, Passmore LH, Bowman RV, Fong KM. MicroRNA-218 is deleted and downregulated in lung squamous cell carcinoma. PLoS ONE. 2010. 5:e12560.

72. Cho JH, Gelinas R, Wang K, Eheridge A, Piper MG, Batte K, Dakhallah D, Price J, Bomman D, Zhang S, Marsh C, Galas D. Systems biology of interstitial lung diseases: integration of microRNA expression. BMC Med Genomics. 2011. 4:8.

73. Pandit KV, Milosevic J, Kaminski N. MicroRNAs in idiopathic pulmonary fibrosis. Transl Res. 2011. 157:191–199.

74. Bouros D, Nicholson AC, Polychronopoulos V, du Bois RM. Acute interstitial pneumonia. Eur Respir J. 2000. 15:412–418.

75. Berkhout B, Jeang KT. RISCy business: MicroRNAs, pathogenesis, and viruses. J Biol Chem. 2007. 282:26641–26645.

76. Lecellier CH, Dunoyer P, Arar K, Lehmann-Che J, Eyquem S, Himber C, Saib A, Voinnet O. A cellular microRNA mediates antiviral defense in human cells. Science. 2005. 308:557–560.

77. Ghosh Z, Mallick B, Chakrabarti J. Cellular versus viral microRNAS in host-virus interaction. Nucl Acids Res. 2009. 37:1035–1048.

78. Jin WB, Wu FL, Kong D, Guo AG. HBV-encoded microRNA candidate and its target. Comput Biol Chem. 2007. 31:124–126.

79. Lee SO, Masyuk T, Splinter P, Banales JM, Masyuk A, Stroope A, Larusso N. MicroRNA15a modulates expression of the cell-cycle regulator Cdc25A and affects hepatic cystogenesis in a rat model of polycystic kidney disease. J Clin Invest. 2008. 118:3714–3724.

80. Chu AS, Firedman JR. A role for microRNA in cystic liver and kidney diseases. J Clin Invest. 2008. 118:3585–3587.

81. Wang K, Zhang S, Marzolf B, Troisch P, Brightman A, Hu Z, Hood LE, Galas DJ. Circulating microRNAs, potential biomarker for drug-induced liver injury. Proc Natl Acad Sci. 2009. 106:4402–4407.

82. Dolganiuc A, Petrasek J, Kodys K, Catalano D, Mandrekar P, Velayudham A, Szabo O. MicroRNA expression profile in Lieber-DeCarlie diet induced alcoholic and methionine choline deficient diet-induced nonalcoholic steatohepatitis models in mice. Alcohol Clin Exp Res. 2009. 33:1704–1710.

83. Skalsky RL, Cullen BR. Viruses, microRNAs, and host interactions. Annu Rev Microbiol. 2010. 64:123–141.

84. Grundhoff A, Sullivan CS. Virus-encoded microRNAs. Virology. 2011. 411:325–343.

85. Grassmann R, Jeang KT. The roles of microRNAs in mammalian virus infection. Biochim Biophys Acta. 2008. 1779:706–711.

86. Gottwein E, Cullen BR. Viral and cellular microRNAs as determinants of viral pathogenesis and immunity. Cell Host Microbe. 2008. 3:375–387.

87. Sonkoly E, Stahle M, Pivarcse A. MicroRNAs and immunity: Novel players in the regulation of normal immune function and inflammation. Semin Cancer Biol. 2008. 18:131–140.

88. Pfeffer S, Zavolan M, Grasser FA, Chien M, Russo JJ, Ju J, John B, Enright AJ, Marks D, Sander C, Tuschl T. Identification of virus-encoded microRNAs. Science. 2004. 304:734–736.

89. Pfeffer S, Sewer A, Lagos-Quintana M, Sheridan R, Sander C, Grässer FA, van Dyk LF, Ho CK, Shuman S, Chien M, Russo JJ, Ju J, Randall G, Lindenbach BD, Rice CM, Simon V, Ho DD, Zavolan M, Tuschl T. Identification of microRNAs of the herpesvirus family. Nat Methods. 2005. 2:269–276.

90. Sullivan CS, Grundhoff AT, Tevethia S, Pipas JM, Ganem D. SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells. Nature. 2005. 435:682–686.

91. Lodish HF, Zhou B, Liu G, Chen CZ. Micromanagement of the immune system by microRNAs. Nat Rev Immunol. 2008. 8:120–130.

92. DiChiara JM, Contreras-Martinez LM, Livny J, Smith D, McDonough KA, Belfort M. Multiple small RNAs identified in Mycobacerium bovis BCG are also expressed in Mycobacterium tuberculosis and Mycobacterium smegmatis. Nucleic Acid Res. 2010. 38:4067–4078.

93. Zhang B, Farwell MA. microRNAs: new emerging class of players for disease diagnosis and gene. J Cell Mol Med. 2008. 12:3–21.

94. Gottwein E, Mukherjee N, Saches C, Frenzel C, Majoros WH, Chi JTA, Braich R, Manoharan M, Soutschek J, Ohler U, Cullen BR. A viral microRNA functions as an ortholog of cellular miR-155. Nature. 2007. 450:1096–1099.

95. Huang J, Wang F, Argyris E, Chen K, Liang Z, Tian H, Huang W, Squires K, Verlinghieri G, Zhang H. Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nature Med. 2007. 13:1241–1247.

96. Potenza N, Papa U, Mosca N, Zerbini F, Nobile V, Russo A. Human microRNA hsa-miR-125a-5p interferes with expression of hepatitis B virus surface antigen. Nucleic Acids Res. 2011. 39:5157–5163.

97. Saba R, Goodman CD, Huzarewich RLCH, Robertson C, Booth SA. A miRNA signature of prion induced neurodegeneration. PLoS ONE. 2008. 3:e3652.

98. Fassi Fehri L, Koch M, Belogolova E, Khalil H, Bolz C, Kalali B, Mollenkopf HJ, Beigier-Bompadre M, Karlas A, Schneider T, Churin Y, Gerhard M, Meyer TF. Helicobacter pylori induces miR-155 in T cells in a cAMP-Foxp3-dependent manner. PLoS One. 2010. 5:e9500.

99. Matsushima K, Isomoto H, Inoue N, Nakayama T, Hayashi T, Nakayama M, Nakao K, Hirayama T, Kohno S. MicroRNA signature in Helicobacter pylori-infected gastric mucosa. Int J Cancer. 2011. 128:361–370.

100. Voinnet O. Micro-balancing innate immunity to Salmonella. EMBO J. 2011. 30:1877–1879.