Skip to main content
SpringerLink
Log in
Book cover

miRNomics: MicroRNA Biology and Computational Analysis pp 15–31Cite as

The Role of MicroRNAs in Biological Processes

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1107))

Abstract

MicroRNAs (miRNAs) are tiny regulators of gene expression on the posttranscriptional level. Since the discovery of the first miRNA 20 years ago, thousands of them have been described. The discovered miRNAs have regulatory functions in biological and pathological processes. Biologically, miRNAs have been implicated in development, differentiation, proliferation, apoptosis, and immune responses. In this work, we summarize the role of miRNA in biological processes taking into account the various areas named above.

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

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
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

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Griffiths-Jones S, Grocock RJ, van Dongen S et al (2006) miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 34:D140–D144

    Article  PubMed  CAS  Google Scholar 

  2. Almeida MI, Reis RM, Calin GA (2011) MicroRNA history: discovery, recent applications, and next frontiers. Mutat Res 717:1–8

    Article  PubMed  CAS  Google Scholar 

  3. Wang Z, Chen Z, Gao Y et al (2011) DNA hypermethylation of microRNA-34b/c has prognostic value for stage non-small cell lung cancer. Cancer Biol Ther 11:490–496

    Article  PubMed  CAS  Google Scholar 

  4. Yuan JH, Yang F, Chen BF et al (2011) The histone deacetylase 4/SP1/microrna-200a regulatory network contributes to aberrant histone acetylation in hepatocellular carcinoma. Hepatology 54:2025–2035

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  6. Huang Y, Shen XJ, Zou Q et al (2010) Biological functions of microRNAs. Bioorg Khim 36:747–752

    PubMed  Google Scholar 

  7. Lee CT, Risom T, Strauss WM (2006) MicroRNAs in mammalian development. Birth Defects Res C Embryo Today 78:129–139

    Article  PubMed  CAS  Google Scholar 

  8. Liu J, Carmell MA, Rivas FV et al (2004) Argonaute2 is the catalytic engine of mammalian RNAi. Science 305:1437–1441

    Article  PubMed  CAS  Google Scholar 

  9. Lagos-Quintana M, Rauhut R, Meyer J et al (2003) New microRNAs from mouse and human. RNA 9:175–179

    Article  PubMed  CAS  Google Scholar 

  10. Mineno J, Okamoto S, Ando T et al (2006) The expression profile of microRNAs in mouse embryos. Nucleic Acids Res 34:1765–1771

    Article  PubMed  CAS  Google Scholar 

  11. Suh MR, Lee Y, Kim JY et al (2004) Human embryonic stem cells express a unique set of microRNAs. Dev Biol 270:488–498

    Article  PubMed  CAS  Google Scholar 

  12. Boyer LA, Lee TI, Cole MF et al (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122:947–956

    Article  PubMed  CAS  Google Scholar 

  13. Strauss WM, Chen C, Lee CT et al (2006) Nonrestrictive developmental regulation of microRNA gene expression. Mamm Genome 17:833–840

    Article  PubMed  CAS  Google Scholar 

  14. Chen CZ, Lodish HF (2005) MicroRNAs as regulators of mammalian hematopoiesis. Semin Immunol 17:155–165

    Article  PubMed  CAS  Google Scholar 

  15. Lu J, Qian J, Chen F et al (2005) Differential expression of components of the microRNA machinery during mouse organogenesis. Biochem Biophys Res Commun 334: 319–323

    Article  PubMed  Google Scholar 

  16. Harris KS, Zhang Z, McManus MT et al (2006) Dicer function is essential for lung epithelium morphogenesis. Proc Natl Acad Sci U S A 103:2208–2213

    Article  PubMed  CAS  Google Scholar 

  17. Yi R, O’Carroll D, Pasolli HA et al (2006) Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs. Nat Genet 38:356–362

    Article  PubMed  CAS  Google Scholar 

  18. Brittis PA, Lu Q, Flanagan JG (2002) Axonal protein synthesis provides a mechanism for localized regulation at an intermediate target. Cell 110:223–235

    Article  PubMed  CAS  Google Scholar 

  19. Giraldez AJ, Cinalli RM, Glasner ME et al (2005) MicroRNAs regulate brain morphogenesis in zebrafish. Science 308:833–838

    Article  PubMed  CAS  Google Scholar 

  20. Lagos-Quintana M, Rauhut R, Yalcin A et al (2002) Identification of tissue-specific microRNAs from mouse. Curr Biol 12:735–739

    Article  PubMed  CAS  Google Scholar 

  21. Krichevsky AM, King KS, Donahue CP et al (2003) A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 9:1274–1281

    Article  PubMed  CAS  Google Scholar 

  22. Smirnova L, Grafe A, Seiler A et al (2005) Regulation of miRNA expression during neural cell specification. Eur J Neurosci 21:1469–1477

    Article  PubMed  Google Scholar 

  23. Schratt GM, Tuebing F, Nigh EA et al (2006) A brain-specific microRNA regulates dendritic spine development. Nature 439:283–289

    Article  PubMed  CAS  Google Scholar 

  24. Sokol NS (2012) The role of microRNAs in muscle development. Curr Top Dev Biol 99:59–78

    Article  PubMed  CAS  Google Scholar 

  25. Bueno MJ, Malumbres M (2011) MicroRNAs and the cell cycle. Biochim Biophys Acta 1812:592–601

    Article  PubMed  CAS  Google Scholar 

  26. Lujambio A, Ropero S, Ballestar E et al (2007) Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res 67:1424–1429

    Article  PubMed  CAS  Google Scholar 

  27. Volinia S, Calin GA, Liu CG et al (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 103:2257–2261

    Article  PubMed  CAS  Google Scholar 

  28. Malhas A, Saunders NJ, Vaux DJ (2010) The nuclear envelope can control gene expression and cell cycle progression via miRNA regulation. Cell Cycle 9:531–539

    Article  PubMed  CAS  Google Scholar 

  29. Miller TE, Ghoshal K, Ramaswamy B et al (2008) MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J Biol Chem 283:29897–29903

    Article  PubMed  CAS  Google Scholar 

  30. Butz H, Liko I, Czirjak S et al (2010) Down-regulation of Wee1 kinase by a specific subset of microRNA in human sporadic pituitary adenomas. J Clin Endocrinol Metab 95:E181–E191

    Article  PubMed  CAS  Google Scholar 

  31. Glover DM, Hagan IM, Tavares AA (1998) Polo-like kinases: a team that plays throughout mitosis. Genes Dev 12:3777–3787

    Article  PubMed  CAS  Google Scholar 

  32. Shi W, Alajez NM, Bastianutto C et al (2010) Significance of Plk1 regulation by miR-100 in human nasopharyngeal cancer. Int J Cancer 126:2036–2048

    PubMed  CAS  Google Scholar 

  33. O’Donnell KA, Wentzel EA, Zeller KI et al (2005) c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435:839–843

    Article  PubMed  Google Scholar 

  34. Schulte JH, Horn S, Otto T et al (2008) MYCN regulates oncogenic MicroRNAs in neuroblastoma. Int J Cancer 122:699–704

    Article  PubMed  CAS  Google Scholar 

  35. Ma L, Young J, Prabhala H et al (2010) miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol 12:247–256

    PubMed  CAS  Google Scholar 

  36. Chang TC, Yu D, Lee YS et al (2008) Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet 40:43–50

    Article  PubMed  CAS  Google Scholar 

  37. Woods K, Thomson JM, Hammond SM (2007) Direct regulation of an oncogenic micro-RNA cluster by E2F transcription factors. J Biol Chem 282:2130–2134

    Article  PubMed  CAS  Google Scholar 

  38. Petrocca F, Visone R, Onelli MR et al (2008) E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis in gastric cancer. Cancer Cell 13:272–286

    Article  PubMed  CAS  Google Scholar 

  39. Yang X, Feng M, Jiang X et al (2009) miR-449a and miR-449b are direct transcriptional targets of E2F1 and negatively regulate pRb-E2F1 activity through a feedback loop by targeting CDK6 and CDC25A. Genes Dev 23: 2388–2393

    Article  PubMed  CAS  Google Scholar 

  40. Ichimura A, Ruike Y, Terasawa K et al (2011) miRNAs and regulation of cell signaling. FEBS J 278:1610–1618

    Article  PubMed  CAS  Google Scholar 

  41. Inui M, Martello G, Piccolo S (2010) MicroRNA control of signal transduction. Nat Rev Mol Cell Biol 11:252–263

    Article  PubMed  CAS  Google Scholar 

  42. Yang CH, Yue J, Pfeffer SR et al (2011) MicroRNA miR-21 regulates the metastatic behavior of B16 melanoma cells. J Biol Chem 286:39172–39178

    Article  PubMed  CAS  Google Scholar 

  43. Lu Z, Li Y, Takwi A et al (2011) miR-301a as an NF-kappaB activator in pancreatic cancer cells. EMBO J 30:57–67

    Article  PubMed  CAS  Google Scholar 

  44. Ma X, Becker Buscaglia LE, Barker JR et al (2011) MicroRNAs in NF-kappaB signaling. J Mol Cell Biol 3:159–166

    Article  PubMed  CAS  Google Scholar 

  45. Cichocki F, Felices M, McCullar V et al (2011) Cutting edge: microRNA-181 promotes human NK cell development by regulating Notch signaling. J Immunol 187:6171–6175

    Article  PubMed  CAS  Google Scholar 

  46. Ferretti E, De Smaele E, Miele E et al (2008) Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells. EMBO J 27:2616–2627

    Article  PubMed  CAS  Google Scholar 

  47. Liu X, Cheng Y, Chen X et al (2011) MicroRNA-31 regulated by the extracellular regulated kinase is involved in vascular smooth muscle cell growth via large tumor suppressor homolog 2. J Biol Chem 286:42371–42380

    Article  PubMed  CAS  Google Scholar 

  48. Terasawa K, Ichimura A, Sato F et al (2009) Sustained activation of ERK1/2 by NGF induces microRNA-221 and 222 in PC12 cells. FEBS J 276:3269–3276

    Article  PubMed  CAS  Google Scholar 

  49. Taganov KD, Boldin MP, Chang KJ et al (2006) 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 103:12481–12486

    Article  PubMed  CAS  Google Scholar 

  50. Martello G, Zacchigna L, Inui M et al (2007) MicroRNA control of Nodal signalling. Nature 449:183–188

    Article  PubMed  CAS  Google Scholar 

  51. O’Connell RM, Taganov KD, Boldin MP et al (2007) MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A 104:1604–1609

    Article  PubMed  Google Scholar 

  52. Tili E, Michaille JJ, Cimino A et al (2007) 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 179:5082–5089

    PubMed  CAS  Google Scholar 

  53. Cobb BS, Hertweck A, Smith J et al (2006) A role for Dicer in immune regulation. J Exp Med 203:2519–2527

    Article  PubMed  CAS  Google Scholar 

  54. 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  PubMed  CAS  Google Scholar 

  55. Xiao C, Calado DP, Galler G et al (2007) MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell 131:146–159

    Article  PubMed  CAS  Google Scholar 

  56. Jopling CL, Yi M, Lancaster AM et al (2005) Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 309:1577–1581

    Article  PubMed  CAS  Google Scholar 

  57. Lecellier CH, Dunoyer P, Arar K et al (2005) A cellular microRNA mediates antiviral defense in human cells. Science 308:557–560

    Article  PubMed  CAS  Google Scholar 

  58. Otsuka M, Jing Q, Georgel P et al (2007) Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression. Immunity 27:123–134

    Article  PubMed  CAS  Google Scholar 

  59. Triboulet R, Mari B, Lin YL et al (2007) Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science 315:1579–1582

    Article  PubMed  CAS  Google Scholar 

  60. Bennasser Y, Le SY, Benkirane M et al (2005) Evidence that HIV-1 encodes an siRNA and a suppressor of RNA silencing. Immunity 22:607–619

    Article  PubMed  CAS  Google Scholar 

  61. Pedersen IM, Cheng G, Wieland S et al (2007) Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449:919–922

    Article  PubMed  CAS  Google Scholar 

  62. Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473:298–307

    Article  PubMed  CAS  Google Scholar 

  63. Yang WJ, Yang DD, Na S et al (2005) Dicer is required for embryonic angiogenesis during mouse development. J Biol Chem 280: 9330–9335

    Article  PubMed  CAS  Google Scholar 

  64. Suarez Y, Fernandez-Hernando C, Yu J et al (2008) Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis. Proc Natl Acad Sci U S A 105:14082–14087

    Article  PubMed  CAS  Google Scholar 

  65. Wang S, Olson EN (2009) AngiomiRs—key regulators of angiogenesis. Curr Opin Genet Dev 19:205–211

    Article  PubMed  CAS  Google Scholar 

  66. Fish JE, Santoro MM, Morton SU et al (2008) miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell 15:272–284

    Article  PubMed  CAS  Google Scholar 

  67. Poliseno L, Tuccoli A, Mariani L et al (2006) MicroRNAs modulate the angiogenic properties of HUVECs. Blood 108:3068–3071

    Article  PubMed  CAS  Google Scholar 

  68. Hua Z, Lv Q, Ye W et al (2006) MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia. PLoS One 1:e116

    Article  PubMed  Google Scholar 

  69. Zhou Q, Gallagher R, Ufret-Vincenty R et al (2011) Regulation of angiogenesis and choroidal neovascularization by members of microRNA-23 27 24 clusters. Proc Natl Acad Sci U S A 108:8287–8292

    Article  PubMed  CAS  Google Scholar 

  70. Vecchione A, Croce CM (2010) Apoptomirs: small molecules have gained the license to kill. Endocr Relat Cancer 17:F37–F50

    Article  PubMed  CAS  Google Scholar 

  71. Reed JC (1998) Bcl-2 family proteins. Oncogene 17:3225–3236

    Article  PubMed  Google Scholar 

  72. Henry-Mowatt J, Dive C, Martinou JC et al (2004) Role of mitochondrial membrane permeabilization in apoptosis and cancer. Oncogene 23:2850–2860

    Article  PubMed  CAS  Google Scholar 

  73. Ashkenazi A (2002) Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer 2:420–430

    Article  PubMed  CAS  Google Scholar 

  74. Brennecke J, Hipfner DR, Stark A et al (2003) bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113:25–36

    Article  PubMed  CAS  Google Scholar 

  75. Zhang J, Du Y, Wu C et al (2010) Curcumin promotes apoptosis in human lung adenocarcinoma cells through miR-186* signaling pathway. Oncol Rep 24:1217–1223

    PubMed  CAS  Google Scholar 

  76. Qin W, Shi Y, Zhao B et al (2010) miR-24 regulates apoptosis by targeting the open reading frame (ORF) region of FAF1 in cancer cells. PLoS One 5:e9429

    Article  PubMed  Google Scholar 

  77. He B, Xiao J, Ren AJ et al (2011) Role of miR-1 and miR-133a in myocardial ischemic postconditioning. J Biomed Sci 18:22

    Article  PubMed  CAS  Google Scholar 

  78. Walker JC, Harland RM (2009) microRNA-24a is required to repress apoptosis in the developing neural retina. Genes Dev 23: 1046–1051

    Article  PubMed  CAS  Google Scholar 

  79. Shi XB, Xue L, Yang J et al (2007) An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells. Proc Natl Acad Sci U S A 104:19983–19988

    Article  PubMed  CAS  Google Scholar 

  80. Adlakha YK, Saini N (2011) MicroRNA-128 downregulates Bax and induces apoptosis in human embryonic kidney cells. Cell Mol Life Sci 68:1415–1428

    Article  PubMed  CAS  Google Scholar 

  81. Tsang WP, Kwok TT (2008) Let-7a microRNA suppresses therapeutics-induced cancer cell death by targeting caspase-3. Apoptosis 13:1215–1222

    Article  PubMed  CAS  Google Scholar 

  82. Bommer GT, Gerin I, Feng Y et al (2007) p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol 17:1298–1307

    Article  PubMed  CAS  Google Scholar 

  83. Hagman Z, Larne O, Edsjo A et al (2010) miR-34c is downregulated in prostate cancer and exerts tumor suppressive functions. Int J Cancer 127:2768–2776

    Article  PubMed  CAS  Google Scholar 

  84. Cimmino A, Calin GA, Fabbri M et al (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A 102:13944–13949

    Article  PubMed  CAS  Google Scholar 

  85. Chen G, Zhu W, Shi D et al (2010) MicroRNA-181a sensitizes human malignant glioma U87MG cells to radiation by targeting Bcl-2. Oncol Rep 23:997–1003

    PubMed  CAS  Google Scholar 

  86. Lin CJ, Gong HY, Tseng HC et al (2008) miR-122 targets an anti-apoptotic gene, Bcl-w, in human hepatocellular carcinoma cell lines. Biochem Biophys Res Commun 375: 315–320

    Article  PubMed  CAS  Google Scholar 

  87. Crawford M, Batte K, Yu L et al (2009) MicroRNA 133B targets pro-survival molecules MCL-1 and BCL2L2 in lung cancer. Biochem Biophys Res Commun 388: 483–489

    Article  PubMed  CAS  Google Scholar 

  88. Nakano H, Miyazawa T, Kinoshita K et al (2010) Functional screening identifies a microRNA, miR-491 that induces apoptosis by targeting Bcl-X(L) in colorectal cancer cells. Int J Cancer 127:1072–1080

    Article  PubMed  CAS  Google Scholar 

  89. He C, Klionsky DJ (2009) Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 43:67–93

    Article  PubMed  CAS  Google Scholar 

  90. Mizushima N, Levine B, Cuervo AM et al (2008) Autophagy fights disease through cellular self-digestion. Nature 451:1069–1075

    Article  PubMed  CAS  Google Scholar 

  91. Chen N, Debnath J (2010) Autophagy and tumorigenesis. FEBS Lett 584:1427–1435

    Article  PubMed  CAS  Google Scholar 

  92. Chen N, Karantza V (2011) Autophagy as a therapeutic target in cancer. Cancer Biol Ther 11:157–168

    Article  PubMed  Google Scholar 

  93. Zhu H, Wu H, Liu X et al (2009) Regulation of autophagy by a beclin 1-targeted microRNA, miR-30a, in cancer cells. Autophagy 5:816–823

    PubMed  CAS  Google Scholar 

  94. Jegga AG, Schneider L, Ouyang X et al (2011) Systems biology of the autophagy-lysosomal pathway. Autophagy 7:477–489

    Article  PubMed  CAS  Google Scholar 

  95. Xiao J, Zhu X, He B et al (2011) MiR-204 regulates cardiomyocyte autophagy induced by ischemia-reperfusion through LC3-II. J Biomed Sci 18:35

    Article  PubMed  Google Scholar 

  96. Frankel LB, Wen J, Lees M et al (2011) microRNA-101 is a potent inhibitor of autophagy. EMBO J 30:4628–4641

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuroscience, Institute of Health Science, University of Dokuz Eylul, Izmir, Turkey

    Kemal Uğur Tüfekci & Şermin Genç

  2. Department of Internal Medicine, School of Medicine, University of Dokuz Eylul, Izmir, Turkey

    Ralph Leo Johan Meuwissen

Authors
  1. Kemal Uğur Tüfekci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ralph Leo Johan Meuwissen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Şermin Genç
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Dabburiya Village, Israel

    Malik Yousef

  2. Izmir Institute of Technology, Izmir, Turkey

    Jens Allmer

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this protocol

Cite this protocol

Tüfekci, K.U., Meuwissen, R.L.J., Genç, Ş. (2014). The Role of MicroRNAs in Biological Processes. In: Yousef, M., Allmer, J. (eds) miRNomics: MicroRNA Biology and Computational Analysis. Methods in Molecular Biology, vol 1107. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-748-8_2

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-748-8_2

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-747-1

  • Online ISBN: 978-1-62703-748-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation