Skip to main content
SpringerLink
Log in

miRNAs in Human Cancer

  • Protocol
  • First Online:
Next-Generation MicroRNA Expression Profiling Technology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 822))

Abstract

MicroRNAs (miRNAs) are small (∼18–25 nucleotides), endogenous, noncoding RNAs that regulate gene expression in a sequence-specific manner via the degradation of target mRNAs or the inhibition of protein translation. miRNAs are predicted to target up to one-third of all human mRNAs. Each miRNA can target hundreds of transcripts and proteins directly or indirectly, and more than one miRNA can converge on a single target transcript; thus, the potential regulatory circuitry afforded by miRNAs is enormous. Increasing evidence is revealing that the expression of miRNAs is deregulated in cancer. High-throughput miRNA quantification technologies provide powerful tools to study global miRNA profiles. It has become progressively more apparent that, although the number of miRNAs (∼1,000) is much smaller than the number of protein-coding genes (∼22,000), miRNA expression signatures more accurately reflect the developmental lineage and tissue origin of human cancers. Large-scale studies in human cancer have further demonstrated that miRNA expression signatures are associated not only with specific tumor subtypes but also with clinical outcomes.

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

Access this chapter

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

Institutional subscriptions

References

  1. Hanahan D, and Weinberg R A. (2000) The hallmarks of cancer, Cell 100, 57–70.

    Article  PubMed  CAS  Google Scholar 

  2. Calin G A, and Croce C M. (2006) MicroRNA signatures in human cancers, Nat Rev Cancer 6, 857–66.

    Article  PubMed  CAS  Google Scholar 

  3. Esquela-Kerscher A, and Slack F J. (2006) Oncomirs – microRNAs with a role in cancer, Nat Rev Cancer 6, 259–69.

    Article  PubMed  CAS  Google Scholar 

  4. Calin G A, Liu C G, Ferracin M, Hyslop T, Spizzo R, Sevignani C., et al. (2007) Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas, Cancer Cell 12, 215–29.

    Article  PubMed  CAS  Google Scholar 

  5. Bartel D P. (2004) MicroRNAs: genomics, biogenesis, mechanism, and function, Cell 116, 281–97.

    Article  PubMed  CAS  Google Scholar 

  6. Ambros V. (2004) The functions of animal microRNAs, Nature 431, 350–355.

    Article  PubMed  CAS  Google Scholar 

  7. He L, and Hannon G J. (2004) MicroRNAs: small RNAs with a big role in gene regulation, Nat Rev Genet 5, 522–31.

    Article  PubMed  CAS  Google Scholar 

  8. Zamore P D, and Haley B. (2005) Ribo-gnome: the big world of small RNAs, Science 309, 1519–24.

    Article  PubMed  CAS  Google Scholar 

  9. Lu J, Getz G, Miska E A, Alvarez-Saavedra E, Lamb J, Peck D., et al. (2005) MicroRNA expression profiles classify human cancers, Nature 435, 834–8.

    Article  PubMed  CAS  Google Scholar 

  10. Calin G A, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik S E., et al. (2005) A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia, N Engl J Med 353, 1793–801.

    Article  PubMed  CAS  Google Scholar 

  11. Volinia S, Calin G A, Liu C G, Ambs S, Cimmino A, Petrocca F., et al. (2006) A microRNA expression signature of human solid tumors defines cancer gene targets, Proc Natl Acad Sci USA 103, 2257–61.

    Article  PubMed  CAS  Google Scholar 

  12. Saito Y, Liang G, Egger G, Friedman J M, Chuang J C, Coetzee G A, et al. (2006) Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells, Cancer Cell 9, 435–43.

    Article  PubMed  CAS  Google Scholar 

  13. Calin G A, Sevignani C, Dumitru C D, Hyslop T, Noch E, Yendamuri S, et al. (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers, Proc Natl Acad Sci USA 101, 2999–3004.

    Article  PubMed  CAS  Google Scholar 

  14. Zhang L, Huang J, Yang N, Greshock J, Megraw M S, Giannakakis A, et al. (2006) microRNAs exhibit high frequency genomic alterations in human cancer, Proc Natl Acad Sci USA 103, 9136–41.

    Article  PubMed  CAS  Google Scholar 

  15. Fazi F, Racanicchi S, Zardo G, Starnes L M, Mancini M, Travaglini L, et al. (2007) Epigenetic silencing of the myelopoiesis regulator microRNA-223 by the AML1/ETO oncoprotein, Cancer Cell 12, 457–66.

    Article  PubMed  CAS  Google Scholar 

  16. Sevignani C, Calin G A, Nnadi S C, Shimizu M, Davuluri R V, Hyslop T, et al. (2007) MicroRNA genes are frequently located near mouse cancer susceptibility loci, Proc Natl Acad Sci USA 104, 8017–22.

    Article  PubMed  CAS  Google Scholar 

  17. Iorio M V, Visone R, Di Leva G, Donati V, Petrocca F, Casalini P, et al. (2007) MicroRNA signatures in human ovarian cancer, Cancer Res 67, 8699–707.

    Article  PubMed  CAS  Google Scholar 

  18. Lu L, Katsaros D, de la Longrais I A, Sochirca O, and Yu H. (2007) Hypermethylation of let-7a-3 in epithelial ovarian cancer is associated with low insulin-like growth factor-II expression and favorable prognosis, Cancer Res 67, 10117–22.

    Article  PubMed  CAS  Google Scholar 

  19. Shell S, Park S M, Radjabi A R, Schickel R, Kistner E O, Jewell D A, et al. (2007) Let-7 expression defines two differentiation stages of cancer, Proc Natl Acad Sci USA 104, 11400–5.

    Article  PubMed  CAS  Google Scholar 

  20. Yang H, Kong W, He L, Zhao J J, O’Donnell J D, Wang J, et al. (2008) MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN, Cancer Res 68, 425–33.

    Article  PubMed  CAS  Google Scholar 

  21. Zhang L, Volinia S, Bonome T, Calin G A, Greshock J, Yang N, et al. (2008) Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer, Proc Natl Acad Sci USA 105, 7004–9.

    Article  PubMed  CAS  Google Scholar 

  22. Yang N, Kaur S, Volinia S, Greshock J, Lassus H, Hasegawa K, et al. (2008) MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer, Cancer Res 68, 10307–14.

    Article  PubMed  CAS  Google Scholar 

  23. Calin G A, Dumitru C D, Shimizu M, Bichi R, Zupo S, Noch E, et al. (2002) Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia, Proc Natl Acad Sci USA 99, 15524–9.

    Article  PubMed  CAS  Google Scholar 

  24. Chan J A, Krichevsky A M, and Kosik K S. (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells, Cancer Res 65, 6029–33.

    Article  PubMed  CAS  Google Scholar 

  25. He L, Thomson J M, Hemann M T, Hernando-Monge E, Mu D, et al. (2005) A microRNA polycistron as a potential human oncogene, Nature 435, 828–33.

    Article  PubMed  CAS  Google Scholar 

  26. Johnson S M, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, et al. (2005) RAS is regulated by the let-7 microRNA family, Cell 120, 635–47.

    Article  PubMed  CAS  Google Scholar 

  27. O’Donnell K A, Wentzel E A, Zeller K I, Dang C V, and Mendell J T. (2005) c-Myc-regulated microRNAs modulate E2F1 expression, Nature 435, 839–43.

    Article  PubMed  CAS  Google Scholar 

  28. Voorhoeve P M, le Sage C, Schrier M, Gillis A J, Stoop H, Nagel R, et al. (2006) A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors, Cell 124, 1169–81.

    Article  PubMed  CAS  Google Scholar 

  29. He L, He X, Lim L P, de Stanchina E, Xuan Z, Liang Y, et al. (2007) A microRNA component of the p53 tumour suppressor network, Nature 447, 1130–4.

    Article  PubMed  CAS  Google Scholar 

  30. Mayr C, Hemann M T, and Bartel D P. (2007) Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation, Science 315, 1576–9.

    Article  PubMed  CAS  Google Scholar 

  31. Corney D C, Flesken-Nikitin A, Godwin A K, Wang W, and Nikitin A Y. (2007) MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth, Cancer Res 67, 8433–8.

    Article  PubMed  CAS  Google Scholar 

  32. Ma L, Teruya-Feldstein J, and Weinberg R A. (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer, Nature 449, 682–8.

    Article  PubMed  CAS  Google Scholar 

  33. Tavazoie S F, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos P D, et al. (2008) Endogenous human microRNAs that suppress breast cancer metastasis, Nature 451, 147–52.

    Article  PubMed  CAS  Google Scholar 

  34. Varambally S, Cao Q, Mani R S, Shankar S, Wang X, Ateeq B, et al. (2008) Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer, Science 322, 1695–9.

    Article  PubMed  CAS  Google Scholar 

  35. Borchert G M, Lanier W, and Davidson B L. (2006) RNA polymerase III transcribes human microRNAs, Nat Struct Mol Biol 13, 1097–101.

    Article  PubMed  CAS  Google Scholar 

  36. Lee Y, Kim M, Han J, Yeom K H, Lee S, Baek S H, et al. (2004) MicroRNA genes are transcribed by RNA polymerase II, EMBO J 23, 4051–60.

    Article  PubMed  CAS  Google Scholar 

  37. Cai X, Hagedorn C H, and Cullen B R. (2004) Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs, RNA 10, 1957–66.

    Article  PubMed  CAS  Google Scholar 

  38. Denli A M, Tops B B, Plasterk R H, Ketting R F, and Hannon G J. (2004) Processing of primary microRNAs by the Microprocessor complex, Nature 432, 231–5.

    Article  PubMed  CAS  Google Scholar 

  39. Gregory R I, Yan K P, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, et al. (2004) The Microprocessor complex mediates the genesis of microRNAs, Nature 432, 235–40.

    Article  PubMed  CAS  Google Scholar 

  40. Curiel T J, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, et al. (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival, Nat Med 10, 942–9.

    Article  PubMed  CAS  Google Scholar 

  41. Landthaler M, Yalcin A, and Tuschl T. (2004) The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis, Curr Biol 14, 2162–7.

    Article  PubMed  CAS  Google Scholar 

  42. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, et al. (2003) The nuclear RNase III Drosha initiates microRNA processing, Nature 425, 415–9.

    Article  PubMed  CAS  Google Scholar 

  43. Yi R, Qin Y, Macara I G, and Cullen B R. (2003) Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs, Genes Dev 17, 3011–6.

    Article  PubMed  CAS  Google Scholar 

  44. Lund E, Guttinger S, Calado A, Dahlberg J E, and Kutay U. (2004) Nuclear export of microRNA precursors, Science 303, 95–8.

    Article  PubMed  CAS  Google Scholar 

  45. Bohnsack M T, Czaplinski K, and Gorlich D. (2004) Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs, RNA 10, 185–91.

    Article  PubMed  CAS  Google Scholar 

  46. Hutvagner G, McLachlan J, Pasquinelli A E, Balint E, Tuschl T, and Zamore P D. (2001) A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA, Science 293, 834–8.

    Article  PubMed  CAS  Google Scholar 

  47. Ketting R F, Fischer S E, Bernstein E, Sijen T, Hannon G J, and Plasterk R H. (2001) Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans, Genes Dev 15, 2654–9.

    Article  PubMed  CAS  Google Scholar 

  48. Gregory R I, Chendrimada T P, Cooch N, and Shiekhattar R. (2005) Human RISC couples microRNA biogenesis and posttranscriptional gene silencing, Cell 123, 631–40.

    Article  PubMed  CAS  Google Scholar 

  49. Maniataki E, and Mourelatos Z. (2005) A human, ATP-independent, RISC assembly machine fueled by pre-miRNA, Genes Dev 19, 2979–90.

    CAS  Google Scholar 

  50. Schwarz D S, Hutvagner G, Du T, Xu Z, Aronin N, and Zamore P D. (2003) Asymmetry in the assembly of the RNAi enzyme complex, Cell 115, 199–208.

    Article  PubMed  CAS  Google Scholar 

  51. Du T, and Zamore P D. (2005) microPrimer: the biogenesis and function of microRNA, Development 132, 4645–52.

    Article  PubMed  CAS  Google Scholar 

  52. Pillai R S, Bhattacharyya S N, and Filipowicz W. (2007) Repression of protein synthesis by miRNAs: how many mechanisms? Trends Cell Biol 17, 118–26.

    Article  PubMed  CAS  Google Scholar 

  53. Standart N, and Jackson R J. (2007) MicroRNAs repress translation of m7Gppp-capped target mRNAs in vitro by inhibiting initiation and promoting deadenylation, Genes Dev 21, 1975–82.

    Article  PubMed  CAS  Google Scholar 

  54. Wakiyama M, Takimoto K, Ohara O, and Yokoyama S. (2007) Let-7 microRNA-mediated mRNA deadenylation and translational repression in a mammalian cell-free system, Genes Dev 21, 1857–62.

    Article  PubMed  CAS  Google Scholar 

  55. Wang B, Love T M, Call M E, Doench J G, and Novina C D. (2006) Recapitulation of short RNA-directed translational gene silencing in vitro, Mol Cell 22, 553–60.

    Article  PubMed  CAS  Google Scholar 

  56. Mathonnet G, Fabian M R, Svitkin Y V, Parsyan A, Huck L, Murata T, et al. (2007) MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F, Science 317, 1764–7.

    Article  PubMed  CAS  Google Scholar 

  57. Kiriakidou M, Tan G S, Lamprinaki S, De Planell-Saguer M, Nelson P T, and Mourelatos Z. (2007) An mRNA m7G cap binding-like motif within human Ago2 represses translation, Cell 129, 1141–51.

    Article  PubMed  CAS  Google Scholar 

  58. Thermann R, and Hentze M W. (2007) Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation, Nature 447, 875–8.

    Article  PubMed  CAS  Google Scholar 

  59. Cimmino A, Calin G A, Fabbri M, Iorio M V, Ferracin M, Shimizu M, et al. (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2, Proc Natl Acad Sci USA 102, 13944–9.

    Article  PubMed  CAS  Google Scholar 

  60. Michael M Z, SM O C, van Holst Pellekaan N G, Young G P, and James R J. (2003) Reduced accumulation of specific microRNAs in colorectal neoplasia, Mol Cancer Res 1, 882–91.

    Google Scholar 

  61. Iorio M V, Ferracin M, Liu C G, Veronese A, Spizzo R, Sabbioni S, et al. (2005) MicroRNA gene expression deregulation in human breast cancer, Cancer Res 65, 7065–70.

    Article  PubMed  CAS  Google Scholar 

  62. van den Berg A, Kroesen B J, Kooistra K, de Jong D, Briggs J, Blokzijl T, et al. (2003) High expression of B-cell receptor inducible gene BIC in all subtypes of Hodgkin lymphoma, Genes Chromosomes Cancer 37, 20–8.

    Article  PubMed  CAS  Google Scholar 

  63. Metzler M, Wilda M, Busch K, Viehmann S, and Borkhardt A. (2004) High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma, Genes Chromosomes Cancer 39, 167–9.

    Article  PubMed  CAS  Google Scholar 

  64. Kluiver J, Poppema S, de Jong D, Blokzijl T, Harms G, Jacobs S, et al. (2005) BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas, J Pathol 207, 243–9.

    Article  PubMed  CAS  Google Scholar 

  65. Eis P S, Tam W, Sun L, Chadburn A, Li Z, Gomez M F, et al. (2005) Accumulation of miR-155 and BIC RNA in human B cell lymphomas, Proc Natl Acad Sci USA 102, 3627–32.

    Article  PubMed  CAS  Google Scholar 

  66. Chang T C, Yu D, Lee Y S, Wentzel E A, Arking D E, West K M, et al. (2008) Widespread microRNA repression by Myc contributes to tumorigenesis, Nat Genet 40, 43–50.

    Article  PubMed  CAS  Google Scholar 

  67. Giannakakis A, Sandaltzopoulos R, Greshock J, Liang S, Huang J, Hasegawa K, et al. (2007) miR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer, Cancer Biol Ther 7.

    Google Scholar 

  68. Kulshreshtha R, Ferracin M, Wojcik S E, Garzon R, Alder H, Agosto-Perez F J, et al. (2007) A microRNA signature of hypoxia, Mol Cell Biol 27, 1859–67.

    Article  PubMed  CAS  Google Scholar 

  69. Yang N, Coukos G, and Zhang L. (2008) MicroRNA epigenetic alterations in human cancer: one step forward in diagnosis and treatment, Int J Cancer 122, 963–8.

    Article  PubMed  CAS  Google Scholar 

  70. Thomson J M, Newman M, Parker J S, Morin-Kensicki E M, Wright T, and Hammond S M. (2006) Extensive post-transcriptional regulation of microRNAs and its implications for cancer, Genes Dev 20, 2202–7.

    Article  PubMed  CAS  Google Scholar 

  71. Muralidhar B, Goldstein L D, Ng G, Winder D M, Palmer R D, Gooding E L, et al. (2007) Global microRNA profiles in cervical squamous cell carcinoma depend on Drosha expression levels, J Pathol 212, 368–77.

    Article  PubMed  CAS  Google Scholar 

  72. Chiosea S, Jelezcova E, Chandran U, Luo J, Mantha G, Sobol R W, et al. (2007) Overexpression of Dicer in precursor lesions of lung adenocarcinoma, Cancer Res 67, 2345–50.

    Article  PubMed  CAS  Google Scholar 

  73. Chiosea S, Jelezcova E, Chandran U, Acquafondata M, McHale T, Sobol R W, et al. (2006) Up-regulation of dicer, a component of the MicroRNA machinery, in prostate adenocarcinoma, Am J Pathol 169, 1812–20.

    Article  PubMed  CAS  Google Scholar 

  74. Karube Y, Tanaka H, Osada H, Tomida S, Tatematsu Y, Yanagisawa K, et al. (2005) Reduced expression of Dicer associated with poor prognosis in lung cancer patients, Cancer Sci 96, 111–5.

    Article  PubMed  CAS  Google Scholar 

  75. Kumar M S, Lu J, Mercer K L, Golub T R, and Jacks T. (2007) Impaired microRNA processing enhances cellular transformation and tumorigenesis, Nat Genet 39, 673–7.

    Article  PubMed  CAS  Google Scholar 

  76. Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, et al. (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis, Cancer Cell 9, 189–98.

    Article  PubMed  CAS  Google Scholar 

  77. Cummins J M, He Y, Leary R J, Pagliarini R, Diaz L A, Jr., Sjoblom T, et al. (2006) The colorectal microRNAome, Proc Natl Acad Sci USA 103, 3687–92.

    Article  PubMed  CAS  Google Scholar 

  78. Zorn K K, Jazaeri A A, Awtrey C S, Gardner G J, Mok S C, Boyd J, et al. (2003) Choice of normal ovarian control influences determination of differentially expressed genes in ovarian cancer expression profiling studies, Clin Cancer Res 9, 4811–8.

    PubMed  CAS  Google Scholar 

  79. Nam E J, Yoon H, Kim S W, Kim H, Kim Y T, Kim J H, et al. (2008) MicroRNA Expression Profiles in Serous Ovarian Carcinoma, Clin Cancer Res 14, 2690–5.

    Article  PubMed  CAS  Google Scholar 

  80. Bommer G T, Gerin I, Feng Y, Kaczorowski A J, Kuick R, Love R E, et al. (2007) p53-Mediated Activation of miRNA34 Candidate Tumor-Suppressor Genes, Curr Biol 17, 1298–307.

    Article  PubMed  CAS  Google Scholar 

  81. Chang T C, Wentzel E A, Kent O A, Ramachandran K, Mullendore M, Lee K H, et al. (2007) Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis, Mol Cell 26, 745–52.

    Article  PubMed  CAS  Google Scholar 

  82. Raver-Shapira N, Marciano E, Meiri E, Spector Y, Rosenfeld N, Moskovits N, et al. (2007) Transcriptional activation of miR-34a contributes to p53-mediated apoptosis, Mol Cell 26, 731–43.

    Article  PubMed  CAS  Google Scholar 

  83. Tarasov V, Jung P, Verdoodt B, Lodygin D, Epanchintsev A, Menssen A, et al. (2007) Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest, Cell Cycle 6, 1586–93.

    Article  PubMed  CAS  Google Scholar 

  84. Corney D C, Flesken-Nikitin A, Godwin A K, Wang W, and Nikitin A Y. (2007) MicroRNA-34b and MicroRNA-34c Are Targets of p53 and Cooperate in Control of Cell Proliferation and Adhesion-Independent Growth, Cancer Res 67, 8433–8.

    Article  PubMed  CAS  Google Scholar 

  85. He L, He X, Lowe S W, and Hannon G J. (2007) microRNAs join the p53 network--another piece in the tumour-suppression puzzle, Nat Rev Cancer 7, 819–22.

    Article  PubMed  CAS  Google Scholar 

  86. Camps C, Buffa F M, Colella S, Moore J, Sotiriou C, Sheldon H, et al. (2008) hsa-miR-210 Is induced by hypoxia and is an independent prognostic factor in breast cancer, Clin Cancer Res 14, 1340–8.

    Article  PubMed  CAS  Google Scholar 

  87. Egger G, Liang G, Aparicio A, and Jones P A. (2004) Epigenetics in human disease and prospects for epigenetic therapy, Nature 429, 457–63.

    Article  PubMed  CAS  Google Scholar 

  88. Scott G K, Mattie M D, Berger C E, Benz S C, and Benz C C. (2006) Rapid alteration of microRNA levels by histone deacetylase inhibition, Cancer Res 66, 1277–81.

    Article  PubMed  CAS  Google Scholar 

  89. Diederichs S, and Haber D A. (2006) Sequence Variations of MicroRNAs in Human Cancer: Alterations in Predicted Secondary Structure Do Not Affect Processing, Cancer Res 66, 6097–104.

    Article  PubMed  CAS  Google Scholar 

  90. Pinkel D, and Albertson D G. (2005) Array comparative genomic hybridization and its applications in cancer, Nat Genet 37 Suppl, S11–7.

    Article  PubMed  CAS  Google Scholar 

  91. Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli M C, and degli Uberti E C. (2005) miR-15a and miR-16-1 down-regulation in pituitary adenomas, J Cell Physiol 204, 280–5.

    Google Scholar 

  92. Ota A, Tagawa H, Karnan S, Tsuzuki S, Karpas A, Kira S, et al. (2004) Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma, Cancer Res 64, 3087–95.

    Article  PubMed  CAS  Google Scholar 

  93. Tagawa H, and Seto M. (2005) A microRNA cluster as a target of genomic amplification in malignant lymphoma, Leukemia 19, 2013–6.

    Article  PubMed  CAS  Google Scholar 

  94. Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, et al. (2005) A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation, Cancer Res 65, 9628–32.

    Article  PubMed  CAS  Google Scholar 

  95. Dews M, Homayouni A, Yu D, Murphy D, Sevignani C, Wentzel E, et al. (2006) Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster, Nat Genet. 38, 1060–5.

    Article  PubMed  CAS  Google Scholar 

  96. Weiler J, Hunziker J, and Hall J. (2006) Anti-miRNA oligonucleotides (AMOs): ammunition to target miRNAs implicated in human disease?, Gene Ther 13, 496–502.

    Article  PubMed  CAS  Google Scholar 

  97. Vester B, and Wengel J. (2004) LNA (locked nucleic acid): high-affinity targeting of complementary RNA and DNA, Biochemistry 43, 13233–41.

    Article  PubMed  CAS  Google Scholar 

  98. Elmen J, Lindow M, Schutz S, Lawrence M, Petri A, Obad S, et al. (2008) LNA-mediated microRNA silencing in non-human primates, Nature 452, 896–9.

    Article  PubMed  CAS  Google Scholar 

  99. Flynt A S, Li N, Thatcher E J, Solnica-Krezel L, and Patton J G. (2007) Zebrafish miR-214 modulates Hedgehog signaling to specify muscle cell fate, Nat Genet 39, 259–63.

    Article  PubMed  CAS  Google Scholar 

  100. Krutzfeldt J, Rajewsky N, Braich R, Rajeev K G, Tuschl T, Manoharan M, et al. (2005) Silencing of microRNAs in vivo with ‘antagomirs’, Nature 438, 685–9.

    Article  PubMed  CAS  Google Scholar 

  101. Esau C, Davis S, Murray S F, Yu X X, Pandey S K, Pear M, et al. (2006) miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting, Cell Metab 3, 87–98.

    Article  PubMed  CAS  Google Scholar 

  102. Hutvagner G, Simard M J, Mello C C, and Zamore P D. (2004) Sequence-specific inhibition of small RNA function, PLoS Biol 2, E98.

    Article  PubMed  Google Scholar 

  103. Vermeulen A, Robertson B, Dalby A B, Marshall W S, Karpilow J, Leake D, et al. (2007) Double-stranded regions are essential design components of potent inhibitors of RISC function, RNA 13, 723–30.

    Article  CAS  PubMed  Google Scholar 

  104. Agirre X, Vilas-Zornoza A, Jimenez-Velasco A, Martin-Subero J I, Cordeu L, Garate L, et al. (2009) Epigenetic silencing of the tumor suppressor microRNA Hsa-miR-124a regulates CDK6 expression and confers a poor prognosis in acute lymphoblastic leukemia, Cancer Res 69, 4443–53.

    Article  PubMed  CAS  Google Scholar 

  105. Kota J, Chivukula R R, O’Donnell K A, Wentzel E A, Montgomery C L, Hwang H-W, et al. (2009) Therapeutic microRNA Delivery Suppresses Tumorigenesis in a Murine Liver Cancer Model, Cell 137, 1005–17.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported in part by grants from the Breast Cancer Alliance, the Ovarian Cancer Research Fund (Liz Tilberis Scholar), the Mary Kay Ash Charitable Foundation, the National Cancer Institute (R01CA142776 and Ovarian Cancer SPORE P50-CA83638-7951 project 3), and the US Department of Defense (W81XWH-10-1-0082).

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Center for Research on Early Detection and Cure of Ovarian Cancer, University of Pennsylvania, Philadelphia, PA, USA

    Xiaomin Zhong, George Coukos & Lin Zhang

Authors
  1. Xiaomin Zhong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. George Coukos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lin Zhang .

Editor information

Editors and Affiliations

  1. Illumina, Inc., Towne Centre Drive 9885, San Diego, 92121, California, USA

    Jian-Bing Fan

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Zhong, X., Coukos, G., Zhang, L. (2012). miRNAs in Human Cancer. In: Fan, JB. (eds) Next-Generation MicroRNA Expression Profiling Technology. Methods in Molecular Biology, vol 822. Humana Press. https://doi.org/10.1007/978-1-61779-427-8_21

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-427-8_21

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-426-1

  • Online ISBN: 978-1-61779-427-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation