Skip to main content
SpringerLink
Log in
Book cover

Programmed Cell Death in Cancer Progression and Therapy pp 299–329Cite as

RNA Interference and Cancer: Endogenous Pathways and Therapeutic Approaches

  • Chapter

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 615))

The endogenous RNA interference (RNAi) pathway regulates cellular differentiation and development using small noncoding hairpin RNAs, called microRNAs. This chapter will review the link between mammalian microRNAs and genes involved in cellular proliferation, differentiation, and apoptosis. Some microRNAs act as oncogenes or tumor suppressor genes, but the target gene networks they regulate are just beginning to be described. Cancer cells have altered patterns of microRNA expression, which can be used to identify the cell of origin and to subtype cancers. RNAi has also been used to identify novel genes involved in cellular transformation using forward genetic screening methods previously only possible in invertebrates. Possible strategies and obstacles to harnessing RNAi for cancer therapy will also be discussed.

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   169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ambros, V. (2004). The functions of animal microRNAs. Nature 431(7006), 350–355.

    CAS  Google Scholar 

  2. Bartel, D. P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2), 281–297.

    CAS  Google Scholar 

  3. Wienholds, E. and Plasterk, R. H. (2005). MicroRNA function in animal development. FEBS Lett 579(26), 5911–5922.

    CAS  Google Scholar 

  4. Du, T. and Zamore, P. D. (2005). microPrimer: the biogenesis and function of microRNA. Development 132(21), 4645–4652.

    CAS  Google Scholar 

  5. Croce, C. M. and Calin, G. A. (2005). miRNAs, cancer, and stem cell division. Cell 122(1), 6–7.

    CAS  Google Scholar 

  6. S. M. Hammond, S. M. (2006). MicroRNAs as oncogenes. Curr Opin Genet Dev 16(1), 4–9.

    CAS  Google Scholar 

  7. Gregory, R. I. and Shiekhattar, R. (2005). MicroRNA biogenesis and cancer. Cancer Res 65(9), 3509–3512.

    CAS  Google Scholar 

  8. Esquela-Kerscher, A. and Slack, F. J. (2006). Oncomirs–microRNAs with a role in cancer. Nat Rev Cancer 6(4), 259–269.

    CAS  Google Scholar 

  9. 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(12), 1957–1966.

    CAS  Google Scholar 

  10. Lee, Y., Kim, M., Han, J., Yeom, K. H., Lee, S., Baek, S. H., and Kim, V. N. (2004). MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23(20), 4051–4060.

    CAS  Google Scholar 

  11. Parizotto, E. A., Dunoyer, P., Rahm, N., Himber, C., and Voinnet, O. (2004). In vivo investigation of the transcription, processing, endonucleolytic activity, and functional relevance of the spatial distribution of a plant miRNA. Genes Dev 18(18), 2237–2242.

    CAS  Google Scholar 

  12. Reinhart, B. J., Weinstein, E. G., Rhoades, M. W., Bartel, B., and Bartel, D. P. (2002). MicroRNAs in plants. Genes Dev 16(13), 1616–1626.

    CAS  Google Scholar 

  13. Lagos-Quintana, M., Rauhut, R., Lendeckel, W., and Tuschl, T. (2001). Identification of novel genes coding for small expressed RNAs. Science 294(5543), 853–858.

    CAS  Google Scholar 

  14. Lau, N. C., Lim, L. P., Weinstein, E. G., and Bartel, D. P. (2001). An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294(5543), 858–862.

    Google Scholar 

  15. Lee, Y., Jeon, K., Lee, J. T., Kim, S., and Kim, V. N. (2002).MicroRNA maturation: stepwise processing and subcellular localization. EMBO J 21(17), 4663–4670.

    CAS  Google Scholar 

  16. Rodriguez, A., Griffiths-Jones, S., Ashurst, J. L., and Bradley, A. (2004). Identification of mammalian microRNA host genes and transcription units. Genome Res 14(10A), 1902–1910.

    Google Scholar 

  17. 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(7014), 231–235.

    Google Scholar 

  18. Lee, Y., Ahn, C., Han, J., Choi, H., Kim, J., Yim, J., Lee, J., Provost, P., Radmark, O., Kim, S., and Kim, V. N. (2003). The nuclear RNase III Drosha initiates microRNA processing. Nature 425(6956), 415–419.

    CAS  Google Scholar 

  19. Gregory, R. I., Yan, K. P., Amuthan, G., Chendrimada, T., Doratotaj, B., Cooch, N., and Shiekhattar, R. (2004). The Microprocessor complex mediates the genesis of microRNAs. Nature 432(7014), 235–240.

    CAS  Google Scholar 

  20. Han, J., Lee, Y., Yeom, K. H., Kim, Y. K., Jin, H., and Kim, V. N. (2004).The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev 18(24), 3016–3027.

    Google Scholar 

  21. 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(23), 2162–2167.

    CAS  Google Scholar 

  22. 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(2), 185–191.

    Google Scholar 

  23. Lund, E., Guttinger, S., Calado, A., Dahlberg, J. E., and Kutay, U. (2004). Nuclear export of microRNA precursors, Science 303(5654), 95–98.

    CAS  Google Scholar 

  24. Zeng, Y., and Cullen, B. R. (2004).Structural requirements for pre-microRNA binding and nuclear export by Exportin 5. Nucleic Acids Res 32(16), 4776–4785.

    Google Scholar 

  25. 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(24), 3011–3016 (2003).

    CAS  Google Scholar 

  26. Bernstein, E., Caudy, A. A., Hammond, S. M., and Hannon, G. J. (2001). Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409(6818), 363–366.

    Google Scholar 

  27. 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(5531), 834–838.

    CAS  Google Scholar 

  28. Chendrimada, T. P., Gregory, R. I., Kumaraswamy, E., Norman, J., Cooch, N., Nishikura, K., and Shiekhattar, R. (2005). TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 436(7051), 740–744.

    CAS  Google Scholar 

  29. Forstemann, K., Tomari, Y., Du, T., Vagin, V. V., Denli, A. M., Bratu, D. P., Klattenhoff, C., Theurkauf, W. E., and Zamore, P. D. (2005). Normal microRNA maturation and germ-line stem cell maintenance requires Loquacious, a double-stranded RNA-binding domain protein. PLoS Biol 3(7), e236.

    Google Scholar 

  30. Jiang, F., Ye, X., Liu, X., Fincher, L., McKearin, D., and Liu, Q. (2005). Dicer-1 and R3D1-L catalyze microRNA maturation in Drosophila. Genes Dev 19(14), 1674–1679.

    CAS  Google Scholar 

  31. Saito, K., Ishizuka, A., Siomi, H., and Siomi, M. C. (2005). Processing of pre-microRNAs by the Dicer-1-Loquacious complex in Drosophila cells. PLoS Biol 3(7), e235.

    Google Scholar 

  32. 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(2), 199–208.

    CAS  Google Scholar 

  33. Khvorova, A., Reynolds, A., and Jayasena, S. D. (2003). Functional siRNAs and miRNAs exhibit strand bias. Cell 115(2), 209–216.

    CAS  Google Scholar 

  34. Rand, T. A., Petersen, S., Du, F., and Wang, X. (2005). Argonaute2 cleaves the anti-guide strand of siRNA during RISC activation. Cell 123(4), 621–629.

    CAS  Google Scholar 

  35. Matranga, C., Tomari, Y., Shin, C., Bartel, D. P., and Zamore, P. D. (2005). Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 123(4), 607–620.

    CAS  Google Scholar 

  36. Rand, T. A., Ginalski, K., Grishin, N. V., and Wang, X. (2004). Biochemical identification of Argonaute 2 as the sole protein required for RNA-induced silencing complex activity. Proc Natl Acad Sci USA 101(40), 14385–14389.

    CAS  Google Scholar 

  37. Hutvagner, G. and Zamore, P. D. (2002). A microRNA in a multiple-turnover RNAi enzyme complex. Science 297(5589), 2056–2060.

    CAS  Google Scholar 

  38. Lippman, Z. and Martienssen, R. (2004). The role of RNA interference in heterochromatic silencing. Nature 431(7006), 364–370.

    CAS  Google Scholar 

  39. Kanellopoulou, C., Muljo, S. A., Kung, A. L., Ganesan, S., Drapkin, R., Jenuwein, T., Livingston, D. M., and Rajewsky, K. (2005). Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev 19(4), 489–501.

    CAS  Google Scholar 

  40. Ma, J. B., Yuan, Y. R., Meister, G., Pei, Y., Tuschl, T., and Patel, D. J. (2005). Structural basis for 5t-end-specific recognition of guide RNA by the A. fulgidus Piwi protein. Nature 434(7033), 666–670 (2005).

    Google Scholar 

  41. Lewis, B. P., Burge, C. B., and Bartel, D. P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120(1), 15–20.

    CAS  Google Scholar 

  42. Rehwinkel, J., Behm-Ansmant, I., Gatfield, D., and Izaurralde, E. (2005). A crucial role for GW182 and the DCP1:DCP2 decapping complex in miRNA-mediated gene silencing. RNA 11(11), 1640–1647.

    CAS  Google Scholar 

  43. Sen, G. L. and Blau, H. M. (2005). Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies. Nat Cell Biol 7(6), 633–636.

    CAS  Google Scholar 

  44. Jakymiw, A., Lian, S., Eystathioy, T., Li, S., Satoh, M., Hamel, J. C., Fritzler, M. J., and Chan, E. K. (2005). Disruption of GW bodies impairs mammalian RNA interference, Nat Cell Biol 7(12), 1267–1274.

    Google Scholar 

  45. Liu, J., Rivas, F. V., Wohlschlegel, J., Yates, J. R., III, Parker, R., and Hannon, G. J. (2005). A role for the P-body component GW182 in microRNA function. Nat Cell Biol 7(12), 1161–1166.

    CAS  Google Scholar 

  46. Liu, J., Valencia-Sanchez, M. A., Hannon, G. J., and Parker, R. (2005). MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol 7(7), 719–723.

    CAS  Google Scholar 

  47. Valencia-Sanchez, M. A., Liu, J., Hannon, G. J., and Parker, R. (2006). Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev 20(5), 515–524.

    CAS  Google Scholar 

  48. Teixeira, D., Sheth, U., Valencia-Sanchez, M. A., Brengues, M., and Parker, R. (2005). Processing bodies require RNA for assembly and contain nontranslating mRNAs. RNA 11(4), 371–382.

    CAS  Google Scholar 

  49. Brengues, M., Teixeira, D., and Parker, R. (2005). Movement of eukaryotic mRNAs between polysomes and cytoplasmic processing bodies. Science 310(5747), 486–489.

    CAS  Google Scholar 

  50. Sheth, U. and Parker, R. (2003). Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science 300(5620), 805–808.

    CAS  Google Scholar 

  51. Coller, J. and Parker, R. (2004). Eukaryotic mRNA decapping. Annu Rev Biochem 73, 861–890.

    CAS  Google Scholar 

  52. Lim, L. P., Lau, N. C., Weinstein, E. G., Abdelhakim, A., Yekta, S., Rhoades, M. W., Burge, C. B., and Bartel, D. P. (2003). The microRNAs of Caenorhabditis elegans. Genes Dev 17(8), 991–1008.

    CAS  Google Scholar 

  53. Lim, L. P., Glasner, M. E., Yekta, S., Burge, C. B., and Bartel, D. P. (2003). Vertebrate microRNA genes. Science 299(5612), 1540.

    CAS  Google Scholar 

  54. Bentwich, I., Avniel, A., Karov, Y., Aharonov, R., Gilad, S., Barad, O., Barzilai, A., Einat, P., Einav, U., Meiri, E., Sharon, E., Spector, Y., and Bentwich, Z. (2005). Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 37(7), 766–770.

    CAS  Google Scholar 

  55. Pasquinelli, A. E. and Ruvkun, G. (2002). Control of developmental timing by microRNAs and their targets. Annu Rev Cell Dev Biol 18495–18513.

    Google Scholar 

  56. Mineno, J., Okamoto, S., Ando, T., Sato, M., Chono, H., Izu, H., Takayama, M., Asada, K., Mirochnitchenko, O., Inouye, M., and Kato, I. (2006). The expression profile of microRNAs in mouse embryos. Nucleic Acids Res 34(6), 1765–1771.

    CAS  Google Scholar 

  57. Willmann, M. R., and Poethig, R. S. (2005). Time to grow up: the temporal role of smallRNAs in plants. Curr Opin Plant Biol 8(5), 548–552.

    CAS  Google Scholar 

  58. Aboobaker, A. A., Tomancak, P., Patel, N., Rubin, G. M., and Lai, E. C. (2005). Drosophila microRNAs exhibit diverse spatial expression patterns during embryonic development. Proc Natl Acad Sci USA 102(50), 18017–18022.

    CAS  Google Scholar 

  59. Biemar, F., Zinzen, R., Ronshaugen, M., Sementchenko, V., Manak, J. R., and Levine, M. S. (2005). Spatial regulation of microRNA gene expression in the Drosophila embryo. Proc Natl Acad Sci USA 102(44), 15907–15911.

    CAS  Google Scholar 

  60. Wienholds, E., Kloosterman, W. P., Miska, E., Alvarez-Saavedra, E., Berezikov, E., de Bruijn, E., Horvitz, H. R., Kauppinen, S., and Plasterk, R. H. (2005). MicroRNA expression in zebrafish embryonic development. Science 309(5732), 310–311.

    CAS  Google Scholar 

  61. Aravin, A. A., Lagos-Quintana, M., Yalcin, A., Zavolan, M., Marks, D., Snyder, B., Gaasterland, T., Meyer, J., and Tuschl, T. (2003). The small RNA profile during Drosophila melanogaster development. Dev Cell 5(2), 337–350.

    CAS  Google Scholar 

  62. Houbaviy, H. B., Murray, M. F., and Sharp, P. A. Embryonic stem cell-specific MicroRNAs. Dev Cell 5(2), 351–358 (2003).

    CAS  Google Scholar 

  63. Pasquinelli, A. E. (2002). MicroRNAs: deviants no longer. Trends Genet 18(4), 171–173.

    CAS  Google Scholar 

  64. Plasterk, R. H. (2006). Micro RNAs in animal development. Cell 124(5), 877–881.

    CAS  Google Scholar 

  65. Doench, J. G. and Sharp, P. A. (2004). Specificity of microRNA target selection in translational repression. Genes Dev 18(5), 504–511 (2004).

    CAS  Google Scholar 

  66. Poy, M. N., Eliasson, L., Krutzfeldt, J., Kuwajima, S., Ma, X., Macdonald, P. E., Pfeffer, S., Tuschl, T., Rajewsky, N., Rorsman, P., and Stoffel, M. (2004). A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432(7014), 226–230.

    CAS  Google Scholar 

  67. Brennecke, J., Hipfner, D. R., Stark, A., Russell, R. B., Cohen, S. M. (2003). bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113(1), 25–36.

    CAS  Google Scholar 

  68. Xu, P., Vernooy, S. Y., Guo, M., and Hay, B. A. (2003). The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr Biol 13(9), 790–795.

    CAS  Google Scholar 

  69. Abrahante, J. E., Daul, A. L., Li, M., Volk, M. L., Tennessen, J. M., Miller, E. A., and Rougvie, A. E. (2003). The Caenorhabditis elegans hunchback-like gene lin-57/hbl-1 controls developmental time and is regulated by microRNAs. Dev Cell 4(5), 625–637.

    CAS  Google Scholar 

  70. Lin, S. Y., Johnson, S. M., Abraham, M., Vella, M. C., Pasquinelli, A., Gamberi, C., Gottlieb, E., and Slack, F. J. (2003). The C elegans hunchback homolog, hbl-1, controls temporal patterning and is a probable microRNA target. Dev Cell 4(5), 639–650.

    CAS  Google Scholar 

  71. Calin, G. A., Dumitru, C. D., Shimizu, M., Bichi, R., Zupo, S., Noch, E., Aldler, H., Rattan, S., Keating, M., Rai, K., Rassenti, L., Kipps, T., Negrini, M., Bullrich, F., and Croce, C. M. (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(24), 15524–15529.

    CAS  Google Scholar 

  72. 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(12), 882–891.

    Google Scholar 

  73. Calin, G. A., Sevignani, C., Dumitru, C. D., Hyslop, T., Noch, E., Yendamuri, S., Shimizu, M., Rattan, S., Bullrich, F., Negrini, M., and Croce, C. M. (2004). Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 101(9), 2999–3004.

    CAS  Google Scholar 

  74. Lagos-Quintana, M., Rauhut, R., Yalcin, A., Meyer, J., Lendeckel, W., and Tuschl, T. (2002). Identification of tissue-specific microRNAs from mouse. Curr Biol 12(9), 735–739.

    CAS  Google Scholar 

  75. Tam, W., Ben-Yehuda, D., and Hayward, W. S. (1997). bic, a novel gene activated by proviral insertions in avian leukosis virus-induced lymphomas, is likely to function through its noncoding RNA. Mol Cell Biol 17(3), 1490–1502.

    CAS  Google Scholar 

  76. Kluiver, J., Poppema, S., de Jong, D., Blokzijl, T., Harms, G., Jacobs, S., Kroesen, B. J., and van den Berg, A. (2005). BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas. J Pathol 207(2), 243–249.

    CAS  Google Scholar 

  77. 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(2), 167–169.

    CAS  Google Scholar 

  78. van den Berg, A., Kroesen, B. J., Kooistra, K., de Jong, D., Briggs, J., Blokzijl, T., Jacobs, S., Kluiver, J., Diepstra, A., Maggio, E., and Poppema, S. (2003). High expression of B-cell receptor inducible gene BIC in all subtypes of Hodgkin lymphoma. Genes Chromosomes Cancer 37(1), 20–28 (2003).

    Google Scholar 

  79. Thomson, J. M., Parker, J., Perou, C. M., and Hammond, S. M. (2004). A custom microarray platform for analysis of microRNA gene expression. Nat Methods 1(1), 47–53.

    CAS  Google Scholar 

  80. Nelson, P. T., Baldwin, D. A., Scearce, L. M., Oberholtzer, J. C., Tobias, J. W., and Mourelatos, Z. (2004). Microarray-based, high-throughput gene expression profiling of microRNAs. Nat Methods 1(2), 155–161.

    CAS  Google Scholar 

  81. Babak, T., Zhang, W., Morris, Q., Blencowe, B. J., and Hughes, T. R. (2004). Probing microRNAs with microarrays: tissue specificity and functional inference. RNA 10(11), 1813–1819.

    CAS  Google Scholar 

  82. Sun, Y., Koo, S., White, N., Peralta, E., Esau, C., Dean, N. M., and Perera, R. J. (2004). Development of a micro-array to detect human and mouse microRNAs and characterization of expression in human organs. Nucleic Acids Res 32(22), e188.

    Google Scholar 

  83. Barad, O., Meiri, E., Avniel, A., Aharonov, R., Barzilai, A., Bentwich, I., Einav, U., Gilad, S., Hurban, P., Karov, Y., Lobenhofer, E. K., Sharon, E., Shiboleth, Y. M., Shtutman, M., Bentwich, Z., and Einat, P. (2004). MicroRNA expression detected by oligonucleotide microarrays: system establishment and expression profiling in human tissues. Genome Res 14(12), 2486–2494.

    CAS  Google Scholar 

  84. Liu, C. G., Calin, G. A., Meloon, B., Gamliel, N., Sevignani, C., Ferracin, M., Dumitru, C. D., Shimizu, M., Zupo, S., Dono, M., Alder, H., Bullrich, F., Negrini, M., and Croce, C. M. (2004). An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues. Proc Natl Acad Sci USA 101(26), 9740–9744.

    CAS  Google Scholar 

  85. Calin, G. A., Liu, C. G., Sevignani, C., Ferracin, M., Felli, N., Dumitru, C. D., Shimizu, M., Cimmino, A., Zupo, S., Dono, M., Dell’Aquila, M. L., Alder, H., Rassenti, L., Kipps, T. J., Bullrich, F., Negrini, M., and Croce, C. M. (2004). MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA 101(32), 11755–11760.

    CAS  Google Scholar 

  86. He, L., Thomson, J. M., Hemann, M. T., Hernando-Monge, E., Mu, D., Goodson, S., Powers, S., Cordon-Cardo, C., Lowe, S. W., Hannon, G. J., and Hammond, S. M. (2005). A microRNA polycistron as a potential human oncogene. Nature 435(7043), 828–833.

    CAS  Google Scholar 

  87. Volinia, S., Calin, G. A., Liu, C. G., Ambs, S., Cimmino, A., Petrocca, F., Visone, R., Iorio, M., Roldo, C., Ferracin, M., Prueitt, R. L., Yanaihara, N., Lanza, G., Scarpa, A., Vecchione, A., Negrini, M., Harris, C. C., and Croce, C. M. (2006). A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 103(7), 2257–2261.

    CAS  Google Scholar 

  88. Yanaihara, N., Caplen, N., Bowman, E., Seike, M., Kumamoto, K., Yi, M., Stephens, R. M., Okamoto, A., Yokota, J., Tanaka, T., Calin, G. A., Liu, C. G., Croce, C. M., and Harris, C. C. (2006). Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9(3), 189–198.

    CAS  Google Scholar 

  89. Calin, G. A., Ferracin, M., Cimmino, A., Di Leva, G., Shimizu, M., Wojcik, S. E., Iorio, M. V., Visone, R., Sever, N. I., Fabbri, M., Iuliano, R., Palumbo, T., Pichiorri, F., Roldo, C., Garzon, R., Sevignani, C., Rassenti, L., Alder, H., Volinia, S., Liu, C. G., Kipps, T. J., Negrini, M., and Croce, C. M. (2005). A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med 353(17), 1793–1801.

    CAS  Google Scholar 

  90. Lu, J., Getz, G., Miska, E. A., Alvarez-Saavedra, E., Lamb, J., Peck, D., Sweet-Cordero, A., Ebert, B. L., Mak, R. H., Ferrando, A. A., Downing, J. R., Jacks, T., Horvitz, H. R., and Golub, T. R. (2005). MicroRNA expression profiles classify human cancers. Nature 435(7043), 834–838.

    CAS  Google Scholar 

  91. Thorgeirsson, S. S., Lee, J. S., and Grisham, J. W. (2006). Functional genomics of hepatocellular carcinoma. Hepatology 43(2 Suppl 1), S145–S150.

    Google Scholar 

  92. Takamizawa, J., Konishi, H., Yanagisawa, K., Tomida, S., Osada, H., Endoh, H., Harano, T., Yatabe, Y., Nagino, M., Nimura, Y., Mitsudomi, T., and Takahashi, T. (2004). Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64(11), 3753–3756.

    CAS  Google Scholar 

  93. Johnson, S. M., Grosshans, H., Shingara, J., Byrom, M., Jarvis, R., Cheng, A., Labourier, E., Reinert, K. L., Brown, D., and Slack, F. J. (2005). RAS is regulated by the let-7 microRNA family. Cell 120(5), 635–647.

    CAS  Google Scholar 

  94. 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(7043), 839–843.

    Google Scholar 

  95. Bernstein, E., Kim, S. Y., Carmell, M. A., Murchison, E. P., Alcorn, H., Li, M. Z., Mills, A. A., Elledge, S. J., Anderson, K. V., and Hannon, G. J. (2003). Dicer is essential for mouse development. Nat Genet 35(3), 215–217.

    CAS  Google Scholar 

  96. Muljo, S. A., Ansel, K. M., Kanellopoulou, C., Livingston, D. M., Rao, A., and Rajewsky, K. (2005). Aberrant T cell differentiation in the absence of Dicer. J Exp Med 202(2), 261–269.

    CAS  Google Scholar 

  97. Harfe, B. D., McManus, M. T., Mansfield, J. H., Hornstein, E., and Tabin, C. J. (2005). The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci USA 102(31), 10898–10903.

    CAS  Google Scholar 

  98. Yi, R., O’Carroll, D., Pasolli, H. A., Zhang, Z., Dietrich, F. S., Tarakhovsky, A., and Fuchs, E. (2006). Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs. Nat Genet 38(3), 356–362.

    CAS  Google Scholar 

  99. Chen, C. Z., Li, L., Lodish, H. F., and Bartel, D. P. (2004). MicroRNAs modulate hematopoietic lineage differentiation. Science 303(5654), 83–86.

    CAS  Google Scholar 

  100. Fazi, F., Rosa, A., Fatica, A., Gelmetti, V., De Marchis, M. L., Nervi, C., and Bozzoni, I. (2005). A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell 123(5), 819–831.

    CAS  Google Scholar 

  101. Felli, N., Fontana, L., Pelosi, E., Botta, R., Bonci, D., Facchiano, F., Liuzzi, F., Lulli, V., Morsilli, O., Santoro, S., Valtieri, M., Calin, G. A., Liu, C. G., Sorrentino, A., Croce, C. M., and Peschle, C. (2005). MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci USA 102(50), 18081–18086.

    CAS  Google Scholar 

  102. Garzon, R., Pichiorri, F., Palumbo, T., Iuliano, R., Cimmino, A., Aqeilan, R., Volinia, S., Bhatt, D., Alder, H., Marcucci, G., Calin, G. A., Liu, C. G., Bloomfield, C. D., Andreeff, M., and Croce, C. M. (2006). MicroRNA fingerprints during human megakaryocytopoiesis. Proc Natl Acad Sci USA 103(13), 5078–5083.

    CAS  Google Scholar 

  103. Mansfield, J. H., Harfe, B. D., Nissen, R., Obenauer, J., Srineel, J., Chaudhuri, A., Farzan-Kashani, R., Zuker, M., Pasquinelli, A. E., Ruvkun, G., Sharp, P. A., Tabin, C. J., and McManus, M. T. (2004). MicroRNA-responsive “sensor” transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Nat Genet 36(10), 1079–1083.

    CAS  Google Scholar 

  104. Morgan, R. (2006). Hox genes: a continuation of embryonic patterning? Trends Genet 22(2), 67–69.

    CAS  Google Scholar 

  105. Tanzer, A., Amemiya, C. T., Kim, C. B., and Stadler, P. F. (2005). Evolution of microRNAs located within Hox gene clusters. J Exp Zoolog B Mol Dev Evol 304(1), 75–85.

    Google Scholar 

  106. Yekta, S., Shih, I. H., and Bartel, D. P. (2004). MicroRNA-directed cleavage of HOXB8 mRNA. Science 304(5670), 594–596.

    CAS  Google Scholar 

  107. Hornstein, E., Mansfield, J. H., Yekta, S., Hu, J. K., Harfe, B. D., McManus, M. T., Baskerville, S., Bartel, D. P., and Tabin, C. J. (2005). The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development. Nature 438(7068), 671–674.

    CAS  Google Scholar 

  108. Naguibneva, I., Ameyar-Zazoua, M., Polesskaya, A., Ait-Si-Ali, S., Groisman, R., Souidi, M., Cuvellier, S., and Harel-Bellan, A. (2006). The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation. Nat Cell Biol 8(3), 278–284.

    CAS  Google Scholar 

  109. Yamamoto, M. and Kuroiwa, A. (2003). Hoxa-11 and Hoxa-13 are involved in repression of MyoD during limb muscle development. Dev Growth Differ 45(5–6), 485–498.

    CAS  Google Scholar 

  110. Yamamoto, M., Gotoh, Y., Tamura, K., Tanaka, M., Kawakami, A., Ide, H., and Kuroiwa, A. (1998). Coordinated expression of Hoxa-11 and Hoxa-13 during limb muscle patterning. Development 125(7), 1325–1335.

    CAS  Google Scholar 

  111. Zhao, Y., Samal, E., and Srivastava, D. (2005). Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis. Nature 436(7048), 214–220.

    CAS  Google Scholar 

  112. Chen, J. F., Mandel, E. M., Thomson, J. M., Wu, Q., Callis, T. E., Hammond, S. M., Conlon, F. L., and Wang, D. Z. (2006). The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 38(2), 228–233.

    CAS  Google Scholar 

  113. Lu, J., McKinsey, T. A., Zhang, C. L., and Olson, E. N. (2000). Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases. Mol Cell 6(2), 233–244.

    CAS  Google Scholar 

  114. Li, S., Czubryt, M. P., McAnally, J., Bassel-Duby, R., Richardson, J. A., Wiebel, F. F., Nordheim, A., and Olson, E. N. (2005). Requirement for serum response factor for skeletal muscle growth and maturation revealed by tissue-specific gene deletion in mice. Proc Natl Acad Sci USA 102(4), 1082–1087.

    CAS  Google Scholar 

  115. Schratt, G. M., Tuebing, F., Nigh, E. A., Kane, C. G., Sabatini, M. E., Kiebler, M., and Greenberg, M. E. (2006). A brain-specific microRNA regulates dendritic spine development. Nature 439(7074), 283–289.

    CAS  Google Scholar 

  116. Bamburg, J. R. (1999). Proteins of the ADF/cofilin family: essential regulators of actin dynamics. Annu Rev Cell Dev Biol 15185–230.

    Google Scholar 

  117. Esau, C., Kang, X., Peralta, E., Hanson, E., Marcusson, E. G., Ravichandran, L. V., Sun, Y., Koo, S., Perera, R. J., Jain, R., Dean, N. M., Freier, S. M., Bennett, C. F., Lollo, B., and Griffey, R. (2004). MicroRNA-143 regulates adipocyte differentiation. J Biol Chem 279(50), 52361–52365.

    CAS  Google Scholar 

  118. Fearnhead, H. O. (2004). Getting back on track, or what to do when apoptosis is de-railed: recoupling oncogenes to the apoptotic machinery. Cancer Biol Ther 3(1), 21–28.

    Google Scholar 

  119. Leaman, D., Chen, P. Y., Fak, J., Yalcin, A., Pearce, M., Unnerstall, U., Marks, D. S., Sander, C., Tuschl, T., and Gaul, U. (2005). Antisense-mediated depletion reveals essential and specific functions of microRNAs in Drosophila development. Cell 121(7), 1097–1108.

    CAS  Google Scholar 

  120. Nairz, K., Rottig, C., Rintelen, F., Zdobnov, E., Moser, M., and Hafen, E. (2006). Overgrowth caused by misexpression of a microRNA with dispensable wild-type function. Dev Biol 291(2), 314–324.

    CAS  Google Scholar 

  121. Cimmino, A., Calin, G. A., Fabbri, M., Iorio, M. V., Ferracin, M., Shimizu, M., Wojcik, S. E., Aqeilan, R. I., Zupo, S., Dono, M., Rassenti, L., Alder, H., Volinia, S., Liu, C. G., Kipps, T. J., Negrini, M., and Croce, C. M. (2005). miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 102(39), 13944–13949.

    CAS  Google Scholar 

  122. Chan, J. A., Krichevsky, A. M., and Kosik, K. S. (2005). MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65(14), 6029–6033.

    CAS  Google Scholar 

  123. Cheng, A. M., Byrom, M. W., Shelton, J., and Ford, L. P. (2005). Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res 33(4), 1290–1297.

    CAS  Google Scholar 

  124. Aza-Blanc, P., Cooper, C. L., Wagner, K., Batalov, S., Deveraux, Q. L., and Cooke, M. P. (2003). Identification of modulators of TRAIL-induced apoptosis via RNAi-based phenotypic screening. Mol Cell 12(3), 627–637.

    CAS  Google Scholar 

  125. MacKeigan, J. P., Murphy, L. O., and Blenis, J. (2005). Sensitized RNAi screen of human kinases and phosphatases identifies new regulators of apoptosis and chemoresistance. Nat Cell Biol 7(6), 591–600.

    CAS  Google Scholar 

  126. Brummelkamp, T. R., Nijman, S. M., Dirac, A. M., and Bernards, R. (2003). Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB. Nature 424(6950), 797–801.

    CAS  Google Scholar 

  127. Paddison, P. J., Silva, J. M., Conklin, D. S., Schlabach, M., Li, M., Aruleba, S., Balija, V., O’Shaughnessy, A., Gnoj, L., Scobie, K., Chang, K., Westbrook, T., Cleary, M., Sachidanandam, R., McCombie, W. R., Elledge, S. J., and Hannon, G. J. (2004). A resource for large-scale RNA-interference-based screens in mammals. Nature 428(6981), 427–431.

    CAS  Google Scholar 

  128. Moffat, J., Grueneberg, D. A., Yang, X., Kim, S. Y., Kloepfer, A. M., Hinkle, G., Piqani, B., Eisenhaure, T. M., Luo, B., Grenier, J. K., Carpenter, A. E., Foo, S. Y., Stewart, S. A., Stockwell, B. R., Hacohen, N., Hahn, W. C., Lander, E. S., Sabatini, D. M., and Root, D. E. (2006). A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell 124(6), 1283–1298.

    CAS  Google Scholar 

  129. Silva, J. M., Li, M. Z., Chang, K., Ge, W., Golding, M. C., Rickles, R. J., Siolas, D., Hu, G., Paddison, P. J., Schlabach, M. R., Sheth, N., Bradshaw, J., Burchard, J., Kulkarni, A., Cavet, G., Sachidanandam, R., McCombie, W. R., Cleary, M. A., Elledge, S. J., and Hannon, G. J. (2005). Second-generation shRNA libraries covering the mouse and human genomes. Nat Genet 37(11), 1281–1288.

    CAS  Google Scholar 

  130. Kolfschoten, I. G., van Leeuwen, B., Berns, K., Mullenders, J., Beijersbergen, R. L., Bernards, R., Voorhoeve, P. M., and Agami, R. (2005). A genetic screen identifies PITX1 as a suppressor of RAS activity and tumorigenicity. Cell 121(6), 849–858.

    CAS  Google Scholar 

  131. Brummelkamp, T. R., Fabius, A. W., Mullenders, J., Madiredjo, M., Velds, A., Kerkhoven, R. M., Bernards, R., and Beijersbergen, R. L. (2006). An shRNA barcode screen provides insight into cancer cell vulnerability to MDM2 inhibitors. Nat Chem Biol 2(4), 202–206.

    CAS  Google Scholar 

  132. Brummelkamp, T. R., Berns, K., Hijmans, E. M., Mullenders, J., Fabius, A., Heimerikx, M., Velds, A., Kerkhoven, R. M., Madiredjo, M., Bernards, R., and Beijersbergen, R. L. (2004). Functional identification of cancer-relevant genes through large-scale RNA interference screens in mammalian cells. Cold Spring Harb Symp Quant Biol 69439–445.

    Google Scholar 

  133. Berns, K., Hijmans, E. M., Mullenders, J., Brummelkamp, T. R., Velds, A., Heimerikx, M., Kerkhoven, R. M., Madiredjo, M., Nijkamp, W., Weigelt, B., Agami, R., Ge, W., Cavet, G., Linsley, P. S., Beijersbergen, R. L., and Bernards, R. (2004). A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature 428(6981), 431–437.

    CAS  Google Scholar 

  134. Westbrook, T. F., Martin, E. S., Schlabach, M. R., Leng, Y., Liang, A. C., Feng, B., Zhao, J. J., Roberts, T. M., Mandel, G., Hannon, G. J., Depinho, R. A., Chin, L., and Elledge, S. J. (2005). A genetic screen for candidate tumor suppressors identifies REST. Cell 121(6), 837–848.

    CAS  Google Scholar 

  135. Ngo, V. N., Davis, R. E., Lamy, L., Yu, X., Zhao, H., Lenz, G., Lam, L. T., Dave, S., Yang, L., Powell, J., and Staudt, L. M. (2006). A loss-of-function RNA interference screen for molecular targets in cancer. Nature 441(7089), 106–110.

    CAS  Google Scholar 

  136. Voorhoeve, P. M., le Sage, C., Schrier, M., Gillis, A. J., Stoop, H., Nagel, R., Liu, Y. P., van Duijse, J., Drost, J., Griekspoor, A., Zlotorynski, E., Yabuta, N., De Vita, G., Nojima, H., Looijenga, L. H., and Agami, R. (2006). A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell 124(6), 1169–1181.

    CAS  Google Scholar 

  137. Shankar, P., Manjunath, N., and Lieberman, J. (2005). The prospect of silencing disease using RNA interference. JAMA 293(11), 1367–1373.

    CAS  Google Scholar 

  138. Pai, S. I., Lin, Y. Y., Macaes, B., Meneshian, A., Hung, C. F., and Wu, T. C. (2006). Prospects of RNA interference therapy for cancer. Gene Ther 13(6), 464–477.

    CAS  Google Scholar 

  139. Brummelkamp, T. R., Bernards, R., and Agami, R. (2002). Stable suppression of tumorigenicity by virus-mediated RNA interference. Cancer Cell 2(3), 243–247.

    CAS  Google Scholar 

  140. Rubinson, D. A., Dillon, C. P., Kwiatkowski, A. V., Sievers, C., Yang, L., Kopinja, J., Rooney, D. L., Ihrig, M. M., McManus, M. T., Gertler, F. B., Scott, M. L., and Van Parijs, L. (2003). A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. Nat Genet 33(3), 401–406.

    CAS  Google Scholar 

  141. Song, E., Lee, S. K., Dykxhoorn, D. M., Novina, C., Zhang, D., Crawford, K., Cerny, J., Sharp, P. A., Lieberman, J., Manjunath, N., and Shankar, P. (2003). Sustained small interfering RNA-mediated human immunodeficiency virus type 1 inhibition in primary macrophages. J Virol 77(13), 7174–7181.

    CAS  Google Scholar 

  142. Purow, B. W., Haque, R. M., Noel, M. W., Su, Q., Burdick, M. J., Lee, J., Sundaresan, T., Pastorino, S., Park, J. K., Mikolaenko, I., Maric, D., Eberhart, C. G., and Fine, H. A. (2005). Expression of Notch-1 and its ligands, Delta-like-1 and Jagged-1, is critical for glioma cell survival and proliferation. Cancer Res 65(6), 2353–2363.

    CAS  Google Scholar 

  143. Yuan, J., Yan, R., Kramer, A., Eckerdt, F., Roller, M., Kaufmann, M., and Strebhardt, K. Cyclin B1 depletion inhibits proliferation and induces apoptosis in human tumor cells. Oncogene 23(34), 5843–5852 (2004).

    CAS  Google Scholar 

  144. Roberson, R. S., Kussick, S. J., Vallieres, E., Chen, S. Y., and Wu, D. Y. (2005). Escape from therapy-induced accelerated cellular senescence in p53-null lung cancer cells and in human lung cancers. Cancer Res 65(7), 2795–2803.

    CAS  Google Scholar 

  145. Zen, Y., Harada, K., Sasaki, M., Chen, T. C., Chen, M. F., Yeh, T. S., Jan, Y. Y., Huang, S. F., Nimura, Y., and Nakanuma, Y. (2005). Intrahepatic cholangiocarcinoma escapes from growth inhibitory effect of transforming growth factor-beta1 by overexpression of cyclin D1. Lab Invest 85(4), 572–581.

    CAS  Google Scholar 

  146. Xiao, Z., Xue, J., Sowin, T. J., Rosenberg, S. H., and Zhang, H. (2005). A novel mechanism of checkpoint abrogation conferred by Chk1 downregulation. Oncogene 24(8), 1403–1411.

    CAS  Google Scholar 

  147. Takei, Y., Kadomatsu, K., Yuzawa, Y., Matsuo, S., and Muramatsu, T. (2004). A small interfering RNA targeting vascular endothelial growth factor as cancer therapeutics. Cancer Res 64(10), 3365–3370.

    CAS  Google Scholar 

  148. Filleur, S., Courtin, A., Ait-Si-Ali, S., Guglielmi, J., Merle, C., Harel-Bellan, A., Clezardin, P., and Cabon, F. (2003). SiRNA-mediated inhibition of vascular endothelial growth factor severely limits tumor resistance to antiangiogenic thrombospondin-1 and slows tumor vascularization and growth. Cancer Res 63(14), 3919–3922.

    CAS  Google Scholar 

  149. Schiffelers, R. M., Ansari, A., Xu, J., Zhou, Q., Tang, Q., Storm, G., Molema, G., Lu, P. Y., Scaria, P. V., and Woodle, M. C. (2004). Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle. Nucleic Acids Res 32(19), e149.

    Google Scholar 

  150. Kilic, N., Oliveira-Ferrer, L., Wurmbach, J. H., Loges, S., Chalajour, F., Neshat-Vahid, S., Weil, J., Fernando, M., and Ergun, S. (2005). Pro-angiogenic signaling by the endothelial presence of CEACAM1. J Biol Chem 280(3), 2361–2369.

    CAS  Google Scholar 

  151. Liu, N., Bi, F., Pan, Y., Sun, L., Xue, Y., Shi, Y., Yao, X., Zheng, Y., and Fan, D. (2004). Reversal of the malignant phenotype of gastric cancer cells by inhibition of RhoA expression and activity. Clin Cancer Res 10(18 Pt 1), 6239–6247.

    Google Scholar 

  152. Chen, Y., Stamatoyannopoulos, G., and Song, C. Z. (2003). Down-regulation of CXCR4 by inducible small interfering RNA inhibits breast cancer cell invasion in vitro. Cancer Res 63(16), 4801–4804.

    CAS  Google Scholar 

  153. Liang, Z., Yoon, Y., Votaw, J., Goodman, M. M., Williams, L., and Shim, H. (2005). Silencing of CXCR4 blocks breast cancer metastasis. Cancer Res 65(3), 967–971.

    CAS  Google Scholar 

  154. Lee, E. J., Mircean, C., Shmulevich, I., Wang, H., Liu, J., Niemisto, A., Kavanagh, J. J., Lee, J. H., and Zhang, W. (2005). Insulin-like growth factor binding protein 2 promotes ovarian cancer cell invasion. Mol Cancer 4(1), 7.

    Google Scholar 

  155. Yin, Q. and Flemington, E. K. (2006). siRNAs against the Epstein Barr virus latency replication factor, EBNA1, inhibit its function and growth of EBV-dependent tumor cells. Virology 346(2), 385–393.

    CAS  Google Scholar 

  156. Hong, M., Murai, Y., Kutsuna, T., Takahashi, H., Nomoto, K., Cheng, C. M., Ishizawa, S., Zhao, Q. L., Ogawa, R., Harmon, B. V., Tsuneyama, K., and Takano, Y. (2006). Suppression of Epstein-Barr nuclear antigen 1 (EBNA1) by RNA interference inhibits proliferation of EBV-positive Burkitt’s lymphoma cells. J Cancer Res Clin Oncol 132(1), 1–8.

    CAS  Google Scholar 

  157. Li, X. P., Li, G., Peng, Y., Kung, H. F., and Lin, M. C. (2004). Suppression of Epstein-Barr virus-encoded latent membrane protein-1 by RNA interference inhibits the metastatic potential of nasopharyngeal carcinoma cells. Biochem Biophys Res Commun 315(1), 212–218.

    CAS  Google Scholar 

  158. Jiang, M. and Milner, J. (2005). Selective silencing of viral gene E6 and E7 expression in HPV-positive human cervical carcinoma cells using small interfering RNAs. Methods Mol Biol 292, 401–420.

    CAS  Google Scholar 

  159. Jiang, M. and Milner, J. (2002). Selective silencing of viral gene expression in HPV-positive human cervical carcinoma cells treated with siRNA, a primer of RNA interference. Oncogene 21(39), 6041–6048.

    CAS  Google Scholar 

  160. Wu, H., Hait, W. N., and Yang, J. M. (2003). Small interfering RNA-induced suppression of MDR1 (P-glycoprotein) restores sensitivity to multidrug-resistant cancer cells. Cancer Res 63(7), 1515–1519.

    CAS  Google Scholar 

  161. Stege, A., Priebsch, A., Nieth, C., and Lage, H. (2004). Stable and complete overcoming of MDR1/P-glycoprotein-mediated multidrug resistance in human gastric carcinoma cells by RNA interference Cancer. Gene Ther 11(11), 699–706.

    CAS  Google Scholar 

  162. Nieth, C., Priebsch, A., Stege, A., and Lage, H. (2003). Modulation of the classical multidrug resistance (MDR) phenotype by RNA interference (RNAi). FEBS Lett 545(2–3), 144–150.

    CAS  Google Scholar 

  163. Yague, E., Higgins, C. F., and Raguz, S. (2004). Complete reversal of multidrug resistance by stable expression of small interfering RNAs targeting MDR1. Gene Ther 11(14), 1170–1174.

    CAS  Google Scholar 

  164. Duan, Z., Brakora, K. A., and Seiden, M. V. (2004). Inhibition of ABCB1 (MDR1) and ABCB4 (MDR3) expression by small interfering RNA and reversal of paclitaxel resistance in human ovarian cancer cells. Mol Cancer Ther 3(7), 833–838.

    CAS  Google Scholar 

  165. Peng, Z., Xiao, Z., Wang, Y., Liu, P., Cai, Y., Lu, S., Feng, W., and Han, Z. C. (2004). Reversal of P-glycoprotein-mediated multidrug resistance with small interference RNA (siRNA) in leukemia cells. Cancer Gene Ther 11(11), 707–712.

    CAS  Google Scholar 

  166. Chang, I. Y., Kim, M. H., Kim, H. B., Lee do, Y., Kim, S. H., Kim, H. Y., and You, H. J. (2005). Small interfering RNA-induced suppression of ERCC1 enhances sensitivity of human cancer cells to cisplatin. Biochem Biophys Res Commun 327(1), 225–233.

    Google Scholar 

  167. Dykxhoorn, D. M. and Lieberman, J. (2005). The silent revolution: RNA interference as basic biology, research tool, and therapeutic. Annu Rev Med 56, 401–423.

    CAS  Google Scholar 

  168. Dykxhoorn, D. M., Palliser, D., and Lieberman, J. (2006). The silent treatment: siRNAs as small molecule drugs. Gene Ther 13(6), 541–552.

    CAS  Google Scholar 

  169. Soutschek, J., Akinc, A., Bramlage, B., Charisse, K., Constien, R., Donoghue, M., Elbashir, S., Geick, A., Hadwiger, P., Harborth, J., John, M., Kesavan, V., Lavine, G., Pandey, R. K., Racie, T., Rajeev, K. G., Rohl, I., Toudjarska, I., Wang, G., Wuschko, S., Bumcrot, D., Koteliansky, V., Limmer, S., Manoharan, M., and Vornlocher, H. P. (2004). Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432(7014), 173–178.

    CAS  Google Scholar 

  170. Urban-Klein, B., Werth, S., Abuharbeid, S., Czubayko, F., and Aigner, A. (2005). RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo. Gene Ther 12(5), 461–466.

    CAS  Google Scholar 

  171. Ge, Q., Filip, L., Bai, A., Nguyen, T., Eisen, H. N., and Chen, J. (2004). Inhibition of influenza virus production in virus-infected mice by RNA interference. Proc Natl Acad Sci USA 101(23), 8676–8681.

    CAS  Google Scholar 

  172. Santel, A., Aleku, M., Keil, O., Endruschat, J., Esche, V., Fisch, G., Dames, S., Loffler, K., Fechtner, M., Arnold, W., Giese, K., Klippel, A., and Kaufmann, J. (2006). A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium. Gene Ther 13(16), 1222–1234.

    CAS  Google Scholar 

  173. Santel, A., Aleku, M., Keil, O., Endruschat, J., Esche, V., Durieux, B., Loffler, K., Fechtner, M., Rohl, T., Fisch, G., Dames, S., Arnold, W., Giese, K., Klippel, A., and Kaufmann, J. (2006). RNA interference in the mouse vascular endothelium by systemic administration of siRNA-lipoplexes for cancer therapy, Gene Ther 13(18), 1360–1370.

    CAS  Google Scholar 

  174. Yano, J., Hirabayashi, K., Nakagawa, S., Yamaguchi, T., Nogawa, M., Kashimori, I., Naito, H., Kitagawa, H., Ishiyama, K., Ohgi, T., and Irimura, T. (2004). Antitumor activity of small interfering RNA/cationic liposome complex in mouse models of cancer, Clin Cancer Res 10(22), 7721–7726.

    CAS  Google Scholar 

  175. Morrissey, D. V., Lockridge, J. A., Shaw, L., Blanchard, K., Jensen, K., Breen, W., Hartsough, K., Machemer, L., Radka, S., Jadhav, V., Vaish, N., Zinnen, S., Vargeese, C., Bowman, K., Shaffer, C. S., Jeffs, L. B., Judge, A., MacLachlan, I., and Polisky, B. (2005). Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat Biotechnol 23(8), 1002–1007.

    CAS  Google Scholar 

  176. Song, E., Zhu, P., Lee, S. K., Chowdhury, D., Kussman, S., Dykxhoorn, D. M., Feng, Y., Palliser, D., Weiner, D. B., Shankar, P., Marasco, W. A., and Lieberman, J. (2005). Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat Biotechnol 23(6), 709–717.

    CAS  Google Scholar 

  177. Bagga, S., Bracht, J., Hunter, S., Massirer, K., Holtz, J., Eachus, R., and Pasquinelli, A. E. (2005). Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell 122(4), 553–563.

    CAS  Google Scholar 

  178. Krutzfeldt, J., Rajewsky, N., Braich, R., Rajeev, K. G., Tuschl, T., Manoharan, M., and Stoffel, M. (2005). Silencing of microRNAs in vivo with “antagomirs”. Nature 438(7068), 685–689.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA

    Derek M. Dykxhoorn, Dipanjan Chowdhury & Judy Lieberman

Authors
  1. Derek M. Dykxhoorn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dipanjan Chowdhury
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Judy Lieberman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science + Business Media B.V

About this chapter

Cite this chapter

Dykxhoorn, D.M., Chowdhury, D., Lieberman, J. (2008). RNA Interference and Cancer: Endogenous Pathways and Therapeutic Approaches. In: Programmed Cell Death in Cancer Progression and Therapy. Advances in Experimental Medicine and Biology, vol 615. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6554-5_14

Download citation

Publish with us

Policies and ethics

Search

Navigation