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Genomics and Pharmacogenomics in Anticancer Drug Development and Clinical Response pp 47–56Cite as

MicroRNAs and Discovery of New Targets

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Part of the book series: Cancer Drug Discovery and Development™ ((CDD&D))

Summary

MicroRNAs are endogenous short non-coding RNAs that regulate gene expression mainly at the post-transcriptional level by base pairing to the 3′ untranslated region of target messenger RNAs. At present, hundreds of microRNAs have been identified in humans, and some of them have been revealed to play a critical role especially in the initiation, progression, and malignant potential of various cancers. In this chapter, we discuss the role of microRNAs in cancer and its potential application for cancer therapy.

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References

  1. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004;116:281–297.

    Article  CAS  PubMed  Google Scholar 

  2. Tsuchiya S, Okuno Y, Tsujimoto G. MicroRNA: biogenetic and functional mechanisms and involvements in cell differentiation and cancer. J Pharmacol Sci 2006;101:267–270.

    Article  CAS  PubMed  Google Scholar 

  3. Pasquinelli AE, Reinhart BJ, Slack F et al. Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 2000;408:86–89.

    Article  CAS  PubMed  Google Scholar 

  4. Griffiths-Jones S, Grocock RJ, van Dongen S et al. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 2006;34:D140–144.

    Article  CAS  PubMed  Google Scholar 

  5. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005;120:15–20.

    Article  CAS  PubMed  Google Scholar 

  6. Xie X, Lu J, Kulbokas EJ et al. Systematic discovery of regulatory motifs in human promoters and 3′ UTRs by comparison of several mammals. Nature 2005;434:338–345.

    Article  CAS  PubMed  Google Scholar 

  7. Berezikov E, Guryev V, van de Belt J et al. Phylogenetic shadowing and computational identification of human microRNA genes. Cell 2005;120:21–24.

    Article  CAS  PubMed  Google Scholar 

  8. Esquela-Kerscher A, Slack FJ. Oncomirs: microRNAs with a role in cancer. Nat Rev Cancer 2006;6:259–269.

    Article  CAS  PubMed  Google Scholar 

  9. Calin GA, Croce CM. MicroRNA-cancer connection: the beginning of a new tale. Cancer Res 2006;66:7390–7394.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  11. Rodriguez A, Griffiths-Jones S, Ashurst JL et al. Identification of mammalian microRNA host genes and transcription units. Genome Res 2004;14:1902–1910.

    Article  CAS  PubMed  Google Scholar 

  12. Lagos-Quintana M, Rauhut R, Lendeckel W et al. Identification of novel genes coding for small expressed RNAs. Science 2001;294:853–858.

    Article  CAS  PubMed  Google Scholar 

  13. Lim LP, Glasner ME, Yekta S et al. Vertebrate microRNA genes. Science 2003;299:1540.

    Google Scholar 

  14. Yu J, Wang F, Yang GH et al. Human microRNA clusters: genomic organization and expression profile in leukemia cell lines. Biochem Biophys Res Commun 2006;349:59–68.

    Article  CAS  PubMed  Google Scholar 

  15. Lee Y, Jeon K, Lee JT et al. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J 2002;21:4663–4670.

    Article  CAS  PubMed  Google Scholar 

  16. Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 2004;10:1957–1966.

    Article  CAS  PubMed  Google Scholar 

  17. Lee Y, Kim M, Han J et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J 2004;23:4051–4060.

    Article  CAS  PubMed  Google Scholar 

  18. Lee Y, Ahn C, Han J et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 2003;425:415–419.

    Article  CAS  PubMed  Google Scholar 

  19. Gregory RI, Yan KP, Amuthan G et al. The microprocessor complex mediates the genesis of microRNAs. Nature 2004;432:235–240.

    Article  CAS  PubMed  Google Scholar 

  20. Han J, Lee Y, Yeom KH et al. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell 2006;125:887–901.

    Article  CAS  PubMed  Google Scholar 

  21. Yi R, Qin Y, Macara IG et al. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 2003;17:3011–3016.

    Article  CAS  PubMed  Google Scholar 

  22. Lund E, Guttinger S, Calado A et al. Nuclear export of microRNA precursors. Science 2004;303: 95–98.

    Article  CAS  PubMed  Google Scholar 

  23. Hutvagner G, McLachlan J, Pasquinelli AE et al. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 2001;293:834–838.

    Article  CAS  PubMed  Google Scholar 

  24. Matranga C, Tomari Y, Shin C et al. Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 2005;123:607–620.

    Article  CAS  PubMed  Google Scholar 

  25. Rand TA, Petersen S, Du F et al. Argonaute2 cleaves the anti-guide strand of siRNA during RISC activation. Cell 2005;123:621–629.

    Article  CAS  PubMed  Google Scholar 

  26. Gregory RI, Chendrimada TP, Cooch N et al. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 2005;123:631–640.

    Article  CAS  PubMed  Google Scholar 

  27. Khvorova A, Reynolds A, Jayasena SD. Functional siRNAs and miRNAs exhibit strand bias. Cell 2003;115:209–216.

    Article  CAS  PubMed  Google Scholar 

  28. Schwarz DS, Hutvágner G, Du T et al. Asymmetry in the assembly of the RNAi enzyme complex. Cell 2003;115:199–208.

    Article  CAS  PubMed  Google Scholar 

  29. Chendrimada TP, Gregory RI, Kumaraswamy E et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 2005;436:740–744.

    Article  CAS  PubMed  Google Scholar 

  30. Meister G, Landthaler M, Patkaniowska A et al. Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Mol Cell 2004;15:185–197.

    Article  CAS  PubMed  Google Scholar 

  31. Hutvágner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex. Science 2002;297:2056–2060.

    Article  PubMed  Google Scholar 

  32. Doench JG, Sharp PA. Specificity of microRNA target selection in translational repression. Genes Dev 2004;18:504–511.

    Article  CAS  PubMed  Google Scholar 

  33. Kiriakidou M, Nelson PT, Kouranov A et al. A combined computational–experimental approach predicts human microRNA targets. Genes Dev 2004;18:1165–1178.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  35. Liu CG, Calin GA, Meloon B et al. An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci USA 2004;101:9740–9744.

    Article  CAS  PubMed  Google Scholar 

  36. Lim LP, Lau NC, Garrett-Engele P et al. Microarray analysis shows that some microRNAs down-regulate large numbers of target mRNAs. Nature 2005;433:769–773.

    Article  CAS  PubMed  Google Scholar 

  37. Lu J, Getz G, Miska EA et al. MicroRNA expression profiles classify human cancers. Nature 2005;435:834–838.

    Article  CAS  PubMed  Google Scholar 

  38. Calin GA, Sevignani C, Dumitru CD et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 2004;101:2999–3004.

    Article  CAS  PubMed  Google Scholar 

  39. Calin GA, Dumitru CD, Shimizu M et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2002;99:15524–15529.

    Article  CAS  PubMed  Google Scholar 

  40. Cimmino A, Calin GA, Fabbri M et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 2005;102:13944-13949. Erratum in: Proc Natl Acad Sci USA 2006;103: 2464–2565.

    Article  CAS  PubMed  Google Scholar 

  41. Zhang L, Huang J, Yang N et al. MicroRNAs exhibit high-frequency genomic alterations in human cancer. Proc Natl Acad Sci USA 2006;103:9136–9141.

    Article  CAS  PubMed  Google Scholar 

  42. Hayashita Y, Osada H, Tatematsu Y et al. A polycistronic microRNA cluster, miR-17–92, is over-expressed in human lung cancers and enhances cell proliferation. Cancer Res 2005;65: 9628–9632.

    Article  CAS  PubMed  Google Scholar 

  43. He L, Thomson JM, Hemann MT et al. A microRNA polycistron as a potential human oncogene. Nature 2005;435:828–833.

    Article  CAS  PubMed  Google Scholar 

  44. O'Donnell KA, Wentzel EA, Zeller KI et al. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2005;435:839–843.

    Article  PubMed  Google Scholar 

  45. Dews M, Homayouni A, Yu D et al. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nat Genet 2006;38:1060–1065.

    Article  CAS  PubMed  Google Scholar 

  46. Eis PS, Tam W, Sun L et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci USA 2005;102:3627–3632.

    Article  CAS  PubMed  Google Scholar 

  47. Tam W, Hughes SH, Hayward WS et al. Avian bic, a gene isolated from a common retroviral site in avian leukosis virus-induced lymphomas that encodes a noncoding RNA, cooperates with c-myc in lymphomagenesis and erythroleukemogenesis. J Virol 2002;76:4275–4286.

    Article  CAS  PubMed  Google Scholar 

  48. Costinean S, Zanesi N, Pekarsky Y et al. Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice. Proc Natl Acad Sci USA 2006;103:7024–7029.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  50. He H, Jazdzewski K, Li W et al. The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA 2005;102:19075–19080.

    Article  CAS  PubMed  Google Scholar 

  51. Martin MM, Lee EJ, Buckenberger JA et al. MicroRNA-155 regulates human angiotensin II type 1 receptor expression in fibroblasts. J Biol Chem 2006;281:18277–18284.

    Article  CAS  PubMed  Google Scholar 

  52. Si ML, Zhu S, Wu H et al. miR-21-mediated tumor growth. Oncogene 2007;26:2799–2803.

    Article  CAS  PubMed  Google Scholar 

  53. Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 2005;65:6029–6033.

    Article  CAS  PubMed  Google Scholar 

  54. Meng F, Henson R, Lang M et al. Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology 2006;130:2113–2129.

    Article  CAS  PubMed  Google Scholar 

  55. Iorio MV, Ferracin M, Liu CG et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005;65:7065–7070.

    Article  CAS  PubMed  Google Scholar 

  56. Takamizawa J, Konishi H, Yanagisawa K et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 2004;64:3753–3756.

    Article  CAS  PubMed  Google Scholar 

  57. Johnson SM, Grosshans H, Shingara J et al. RAS is regulated by the let-7 microRNA family. Cell 2005;120:635–647.

    Article  CAS  PubMed  Google Scholar 

  58. Voorhoeve PM, le Sage C, Schrier M et al. A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell 2006;124:1169-1181.

    Article  CAS  PubMed  Google Scholar 

  59. Hahn WC, Counter CM, Lundberg AS et al. Creation of human tumour cells with defined genetic elements. Nature 1999;400:464–468.

    Article  CAS  PubMed  Google Scholar 

  60. Hunter K. Host genetics influence tumour metastasis. Nat Rev Cancer 2006;6:141–146.

    Article  CAS  PubMed  Google Scholar 

  61. Hunter KW, Crawford NP. Germ line polymorphism in metastatic progression. Cancer Res 2006;66:1251–1254.

    Article  CAS  PubMed  Google Scholar 

  62. Calin GA, Ferracin M, Cimmino A et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 2005;353:1793–1801.

    Article  CAS  PubMed  Google Scholar 

  63. Abelson JF, Kwan KY, O'Roak BJ et al. Sequence variants in SLITRK1 are associated with Tourette’s syndrome. Science 2005;310:317–320.

    Article  CAS  PubMed  Google Scholar 

  64. Tsuchiya Y, Nakajima M, Takagi S et al. MicroRNA regulates the expression of human cytochrome P450 1B1. Cancer Res 2006;66:9090–9098.

    Article  CAS  PubMed  Google Scholar 

  65. Ramaswamy S, Tamayo P, Rifkin R et al. Multiclass cancer diagnosis using tumor gene expression signatures. Proc Natl Acad Sci USA 2001;98:15149–15154.

    Article  CAS  PubMed  Google Scholar 

  66. Krutzfeldt J, Rajewsky N, Braich R et al. Silencing of microRNAs in vivo with “antagomirs.” Nature 2005;438:685–689.

    Article  PubMed  Google Scholar 

  67. Esau C, Davis S, Murray SF et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab 2006;3:87–98.

    Article  CAS  PubMed  Google Scholar 

  68. Enright AJ, John B, Gaul U et al. MicroRNA targets in Drosophila. Genome Biol 2003;5:R1.

    Article  PubMed  Google Scholar 

  69. John B, Enright AJ, Aravin A et al. Human microRNA targets. PLoS Biol 2004;2:e363. Erratum in: PLoS Biol 2005;3:e264.

    Article  PubMed  Google Scholar 

  70. Kiriakidou M, Nelson PT, Kouranov A et al. A combined computational–experimental approach predicts human microRNA targets. Genes Dev 2004;18:1165–1178.

    Article  CAS  PubMed  Google Scholar 

  71. Lewis BP, Shih IH, Jones-Rhoades MW et al. Prediction of mammalian microRNA targets. Cell 2003;115:787–798.

    Article  CAS  PubMed  Google Scholar 

  72. Krek A, Grun D, Poy MN et al. Combinatorial microRNA target predictions. Nat Genet 2005;37: 495–500.

    Article  CAS  PubMed  Google Scholar 

  73. Sethupathy P, Megraw M, Hatzigeorgiou AG. A guide through present computational approaches for the identification of mammalian microRNA targets. Nat Methods 2006;3:881–886.

    Article  CAS  PubMed  Google Scholar 

  74. 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;126:1203–1217.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Dr. N. Hirota for her invaluable advice. We apologize for the incompleteness of the referencing due to space limitations and timing.

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Authors and Affiliations

  1. Department of Genomic Drug Discovery Science, Department of PharmacoInformatics, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

    Soken Tsuchiya PharmD

  2. Department of PharmacoInformatics, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

    Yasushi Okuno PharmD

  3. Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan

    Gozoh Tsujimoto MD

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  1. Soken Tsuchiya PharmD
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  2. Yasushi Okuno PharmD
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  3. Gozoh Tsujimoto MD
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Editors and Affiliations

  1. Department of Medicine, Section of Hematology/Oncology, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637-1470, USA

    Federico Innocenti

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© 2008 Humana Press, a part of Springer Science+Business Media, LLC

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Tsuchiya, S., Okuno, Y., Tsujimoto, G. (2008). MicroRNAs and Discovery of New Targets. In: Innocenti, F. (eds) Genomics and Pharmacogenomics in Anticancer Drug Development and Clinical Response. Cancer Drug Discovery and Development™. Humana Press. https://doi.org/10.1007/978-1-60327-088-5_4

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