Skip to main content
SpringerLink
Log in
Book cover

Circulating microRNAs in Disease Diagnostics and their Potential Biological Relevance pp 197–214Cite as

Circulating microRNAs in Inflammatory Bowel Diseases

  • Chapter
  • First Online:

Part of the book series: Experientia Supplementum ((EXS,volume 106))

Abstract

Inflammatory bowel diseases (IBD) are chronic, idiopathic, polygenic diseases with significant genetic heterogeneity. The two major types of IBD are Crohn’s disease (CD) and ulcerative colitis (UlC). It is well known that chronic intestinal inflammation results from the interplay of genetic, immunologic, and environmental factors, so the failure to properly downregulate nonspecific inflammation started by an environmental trigger may lead to the development of IBD. Recent studies indicate several microRNAs (miRNAs) as regulators of important pathways of the immune response and immune cell development, which are crucial to the pathogenesis of a variety of inflammatory diseases, including IBD. Additionally, miRNAs are shown to be crucial regulators of intestinal epithelial barrier function, colonic epithelial cell-derived chemokine expression, and autophagy mechanisms. About 100 miRNAs have been indicated to exhibit altered expression in tissues and blood for UlC and CD, when compared to healthy normal controls. Taking into consideration that to date the diagnosis and follow-up of IBD are performed by invasive colonoscopy, it is well suggested that circulating microRNAs might be promising noninvasive biomarkers for IBD. Therefore, recent studies have focused on comparing miRNAs expression profile in tissue to miRNAs profile in blood, in order to introduce the analysis of circulating microRNAs in the future clinical practice. In this chapter, the role of microRNAs in IBD and the most promising circulating microRNAs will be discussed that could be used as noninvasive biomarkers for IBD diagnosis.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Adams AT, Kennedy NA, Hansen R et al (2014) Two-stage genome-wide methylation profiling in childhood-onset Crohn’s Disease implicates epigenetic alterations at the VMP1/MIR21 and HLA loci. Inflamm Bowel Dis 20:1784–1793

    Article  PubMed  PubMed Central  Google Scholar 

  • Anderson CA, Boucher G, Lees CW et al (2011) Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet 43:246–252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Androulidaki A, Iliopoulos D, Arranz A et al (2009) The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs. Immunity 31:220–231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bazzoni F, Rossato M, Fabbri M et al (2009) Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals. Proc Natl Acad Sci USA 106:5282–5287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bian Z, Li L, Cui J et al (2011) Role of miR-150-targeting c-Myb in colonic epithelial disruption during dextran sulphate sodium-induced murine experimental colitis and human ulcerative colitis. J Pathol 225:544–553

    Article  CAS  PubMed  Google Scholar 

  • Brain O, Owens BM, Pichulik T et al (2013) The intracellular sensor NOD2 induces microRNA-29 expression in human dendritic cells to limit IL-23 release. Immunity 39:521–536

    Article  CAS  PubMed  Google Scholar 

  • Brant SR, Panhuysen CI, Nicolae D et al (2003) MDR1 Ala893 polymorphism is associated with inflammatory bowel disease. Am J Hum Genet 73:1282–1292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brest P, Lapaquette P, Souidi M et al (2011) A synonymous variant in IRGM alters a binding site for miR-196 and causes deregulation of IRGM-dependent xenophagy in Crohn’s disease. Nat Genet 43:242–245

    Article  CAS  PubMed  Google Scholar 

  • Buchner AM, Blonski W, Lichtenstein GR (2011) Update on the management of Crohn’s disease. Curr Gastroenterol Rep 13:465–474

    Article  PubMed  Google Scholar 

  • Chamaillard M, Iacob R, Desreumaux P et al (2006) Advances and perspectives in the genetics of inflammatory bowel disease. Clin Gastroenterol Hepatol 4:143–151

    Article  CAS  PubMed  Google Scholar 

  • Chen CZ, Li L, Lodish HF et al (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–86

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Ge W, Xu L et al (2012) miR- 200b is involved in intestinal fibrosis of Crohn’s disease. Int J Mol Med 29:601–606

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen Y, Wang C, Liu Y et al (2013a) miR-122 targets NOD2 to decrease intestinal epithelial cell injury in Crohn’s disease. Biochem Biophys Res Commun 438:133–139

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Xiao Y, Ge W et al (2013b) miR-200b inhibits TGF-β1-induced epithelial-mesenchymal transition and promotes growth of intestinal epithelial cells. Cell Death Dis 4:e541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Croxford AL, Mair F, Becher B (2012) IL-23: one cytokine in control of autoimmunity. Eur J Immunol 42:2263–2273

    Article  CAS  PubMed  Google Scholar 

  • Duerr RH, Taylor KD, Brant SR et al (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461–1463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duttagupta R, DiRienzo S, Jiang R et al (2012) Genome-wide maps of circulating miRNA biomarkers for ulcerative colitis. PLoS ONE 7, e31241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ek WE, D’Amato M, Halfvarson J (2014) The history of genetics in inflammatory bowel disease. Ann Gastroenterol 27:294–303

    PubMed  PubMed Central  Google Scholar 

  • Escobar TM, Kanellopoulou C, Kugler DG et al (2014) miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve polycomb-mediated repression. Immunity 40:865–879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fasseu M, Tréton X, Guichard C et al (2010) Identification of restricted subsets of mature microRNA abnormally expressed in inactive colonic mucosa of patients with nflammatory bowel disease. PLoS ONE 5, e13160

    Article  PubMed  PubMed Central  Google Scholar 

  • Feng X, Wang H, Ye S et al (2012) Up-regulation of microRNA-126 may contribute to pathogenesis of ulcerative colitis via regulating NF-kappaB inhibitor IκBα. PLoS ONE 7, e52782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fisher SA, Tremelling M, Anderson CA et al (2008) Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn’s disease. Nat Genet 40:710–712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Franchi L, Warner N, Viani K et al (2009) Function of Nod like receptors in microbial recognition and host defense. Immunol Rev 227:106–128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Franke A, McGovern DP, Barrett JC et al (2010) Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat Genet 42:1118–1125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghorpade DS, Sinha AY, Holla S et al (2013) NOD2-nitric oxide-responsive microRNA-146a activates Sonic hedgehog signaling to orchestrate inflammatory responses in murine model of inflammatory bowel disease. J Biol Chem 288:33037–33048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gibbings D, Mostowy S, Jay F et al (2012) Selective autophagy degrades DICER and AGO2 and regulates miRNA activity. Nat Cell Biol 14:1314–1321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang Z, Shi T, Zhou Q et al (2014) miR-141 regulates colonic leukocytic trafficking by targeting CXCL12β during murine colitis and human Crohn’s disease. Gut 63:1247–1257

    Article  CAS  PubMed  Google Scholar 

  • Hugot J-P, Chamaiilard M, Zouali H et al (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411:599–603

    Article  CAS  PubMed  Google Scholar 

  • Iborra M, Bernuzzi F, Correale C et al (2013) Identification of serum and tissue micro-RNA expression profiles in different stages of inflammatory bowel disease. Clin Exp Immunol 73:250–258

    Article  Google Scholar 

  • Jeker LT, Zhou X, Gershberg K et al (2012) MicroRNA 10a marks regulatory T cells. PLoS ONE 7, e36684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang S, Li C, Olive V et al (2011) Molecular dissection of the miR-17-92 cluster’s critical dual roles in promoting Th1 responses and preventing inducible Treg differentiation. Blood 118:5487–5497

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jostins L, Ripke S, Weersma RK et al (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491:119–124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalla R, Ventham NT, Kennedy NA et al (2014) MicroRNAs: new players in IBD. Gut 64:504–517

    Article  PubMed  PubMed Central  Google Scholar 

  • Koukos G, Polytarchou C, Kaplan JL et al (2013) MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of pediatric patients with ulcerative colitis. Gastroenterology 145:842–852e2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Q, Verma IM (2002) NF-kappaB regulation in the immune system. Nat Rev Immunol 2:725–734

    Article  CAS  PubMed  Google Scholar 

  • Li QJ, Chau J, Ebert PJ et al (2007) miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 129:147–161

    Article  CAS  PubMed  Google Scholar 

  • Lu LF, Thai TH, Calado DP et al (2009) Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity 30:80–91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu C, Chen J, Xu HG et al (2014) MIR106B and MIR93 prevent removal of bacteria from epithelial cells by disrupting ATG16L1-mediated autophagy. Gastroenterology 146:188–199

    Article  CAS  PubMed  Google Scholar 

  • Molodecky NA, Soon IS, Rabi DM et al (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142:46–54e42

    Article  PubMed  Google Scholar 

  • Muljo SA, Ansel KM, Kanellopoulou C et al (2005) Aberrant T cell differentiation in the absence of Dicer. J Exp Med 202:261–269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nata T, Fujiya M, Ueno N et al (2013) MicroRNA-146b improves intestinal injury in mouse colitis by activating nuclear factor-κB and improving epithelial barrier function. J Gene Med 15:249–260

    Article  CAS  PubMed  Google Scholar 

  • Nguyen HT, Dalmasso G, Müller S et al (2014) Crohn’s disease-associated adherent invasive Escherichia coli modulate levels of microRNAs in intestinal epithelial cells to reduce autophagy. Gastroenterology 146:508–519

    Article  CAS  PubMed  Google Scholar 

  • Noble CL, Nimmo ER, Drummond H et al (2005) The contribution of OCTN1/2 variants within the IBD5 locus to disease susceptibility and severity in Crohn’s disease. Gastroenterology 129:1854–1864

    Article  CAS  PubMed  Google Scholar 

  • Ogura Y, Bonen DK, Inohara N et al (2001) A frameshift mutation in Nod2 associated with susceptibility to Crohn’s disease. Nature 411:603–606

    Article  CAS  PubMed  Google Scholar 

  • Paraskevi A, Theodoropoulos G, Papaconstantinou I et al (2012) Circulating MicroRNA in inflammatory bowel disease. J Crohns Colitis 6:900–904

    Article  PubMed  Google Scholar 

  • Parkes M, Cortes A, van Heel DA et al (2013) Genetic insights into common pathways and complex relationships among immune-mediated diseases. Nat Rev Genet 14(9):661–673

    Article  CAS  PubMed  Google Scholar 

  • Patel KK, Stappenbeck TS (2013) Autophagy and intestinal homeostasis. Annu Rev Physiol 75:241–262

    Article  CAS  PubMed  Google Scholar 

  • Sartor RB (2006) Mechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol 3(7):390–407

    Article  CAS  PubMed  Google Scholar 

  • Schulte LN, Westermann AJ, Vogel J (2013) Differential activation and functional specialization of miR-146 and miR-155 in innate immune sensing. Nucleic Acids Res 41:542–553

    Article  CAS  PubMed  Google Scholar 

  • Stoll M, Corneliussen B, Costello CM et al (2004) Genetic variation in DLG5 is associated with inflammatory bowel disease. Nat Genet 36:476–480

    Article  CAS  PubMed  Google Scholar 

  • Tang B, Xiao B, Liu Z et al (2010) Identification of MyD88 as a novel target of miR-155, involved in negative regulation of Helicobacter pylori-induced inflammation. FEBS Lett 584:1481–1486

    Article  CAS  PubMed  Google Scholar 

  • Velu VK, Ramesh R, Srinivasan AR (2012) Circulating MicroRNAs as biomarkers in health and disease. J Clin Diagn Res 6:1791–1795

    PubMed  Google Scholar 

  • Westbrook AM, Szakmary A, Schiest RH (2010) Mechanisms of intestinal inflammation and development of associated cancers: lessons learned from mouse models. Mutat Res 705:40–59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu F, Zhang S, Dassopoulos T et al (2010) Identification of microRNAs associated with ileal and colonic Crohn’s disease. Inflamm Bowel Dis 16:1729–1738

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu F, Guo NJ, Tian H et al (2011) Peripheral blood microRNAs distinguish active ulcerative colitis and Crohn's disease. Inflamm Bowel Dis 17:241–250

    Google Scholar 

  • Wu F, Dong F, Arendovich N et al (2014) Divergent influence of microRNA-21 deletion on murine colitis phenotypes. Inflamm Bowel Dis 20:1972–1985

    Article  PubMed  Google Scholar 

  • Xue X, Feng T, Yao S et al (2011) Microbiota downregulates dendritic cell expression of miR-10a, which targets IL-12/IL-23p40. J Immunol 187:5879–5886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Ma Y, Shi C (2013) Overexpression of miR-21 in patients with ulcerative colitis impairs intestinal epithelial barrier function through targeting the Rho GTPase RhoB. Biochem Biophys Res Commun 434:746–752

    Article  CAS  PubMed  Google Scholar 

  • Ye D, Guo S, Al-Sadi R et al (2011) MicroRNA regulation of intestinal epithelial tight junction permeability. Gastroenterology 141:1323–1333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zahm AM, Thayu M, Hand NJ et al (2011) Circulating microRNA is a biomarker of pediatric Crohn disease. J Pediatr Gastroenterol Nutr 53:26–33

    Article  CAS  PubMed  Google Scholar 

  • Zahm AM, Hand NJ, Tsoucas DM et al (2014) Rectal microRNAs are perturbed in pediatric inflammatory bowel disease of the colon. J Crohns Colitis 8:1108–1117

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Medicine, University of Athens, Michalakopoulou 176, 11527, Athens, Greece

    Maria Gazouli Ph.D.

Authors
  1. Maria Gazouli Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria Gazouli Ph.D. .

Editor information

Editors and Affiliations

  1. 2nd Department of Medicine, Semmelweis University, Budapest, Hungary

    Peter Igaz

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Gazouli, M. (2015). Circulating microRNAs in Inflammatory Bowel Diseases. In: Igaz, P. (eds) Circulating microRNAs in Disease Diagnostics and their Potential Biological Relevance. Experientia Supplementum, vol 106. Springer, Basel. https://doi.org/10.1007/978-3-0348-0955-9_9

Download citation

Publish with us

Policies and ethics

Search

Navigation