The AAPS Journal

, 11:747 | Cite as

Therapeutic MicroRNA Strategies in Human Cancer

  • Chunsheng Li
  • Yi Feng
  • George Coukos
  • Lin Zhang
Review Article Theme: siRNA and microRNA: From Target Validation to Therapy


MicroRNAs (miRNAs) are ~22 nucleotide long, noncoding, endogenous RNA molecules which exert their functions by base pairing with messenger RNAs (mRNAs), thereby regulate protein-coding gene expression. In eukaryotic cells, miRNAs play important roles in regulating biological processes such as proliferation, differentiation, apoptosis, and stem cell self-renewal. The human genome may contain as many as 1,000 miRNAs, and more than 700 of them have been identified. miRNAs are predicted to target up to one third of mRNAs. Each miRNA can target hundreds of transcripts directly or indirectly, while more than one miRNA can converge on a single transcript target. Therefore, the potential regulatory circuitry afforded by miRNA is enormous. Recently, mounting evidence implicates miRNAs as a new class of modulator for human tumor initiation and progression. Therefore, it has been proposed that manipulating miRNA activity and miRNA biogenesis may be a novel avenue for developing efficient therapies against cancer.

Key words

cancer microRNA noncoding RNA therapy 



This work was supported by research grants from the Breast Cancer Alliance, the Ovarian Cancer Research Fund, National Cancer Institute and Department of Defense. Many studies greatly contributed to our knowledge on miRNAs and their therapeutic value in cancer treatment, due to the space limitation of this review, we could not cite all these papers. We apologize for that.


  1. 1.
    Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–54.CrossRefPubMedGoogle Scholar
  2. 2.
    Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993 Dec 3;75(5):855–62.CrossRefPubMedGoogle Scholar
  3. 3.
    Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ. miRBase: tools for microRNA genomics. Nucleic Acids Res. 2008 Jan;36(Database issue):D154–8.PubMedGoogle Scholar
  4. 4.
    Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005 Jan 14;120(1):15–20.CrossRefPubMedGoogle Scholar
  5. 5.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004 Jan 23;116(2):281–97.CrossRefPubMedGoogle Scholar
  6. 6.
    Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 2009 Feb;10(2):126–39.CrossRefPubMedGoogle Scholar
  7. 7.
    Carthew RW, Sontheimer EJ. Origins and Mechanisms of miRNAs and siRNAs. Cell. 2009 Feb 20;136(4):642–55.CrossRefPubMedGoogle Scholar
  8. 8.
    Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006 Nov;6(11):857–66.CrossRefPubMedGoogle Scholar
  9. 9.
    Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006 Apr;6(4):259–69.CrossRefPubMedGoogle Scholar
  10. 10.
    Spizzo R, Nicoloso MS, Croce CM, Calin GA. SnapShot: MicroRNAs in Cancer. Cell. 2009 May 1;137(3):586–e1.CrossRefPubMedGoogle Scholar
  11. 11.
    Borchert GM, Lanier W, Davidson BL. RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol. 2006 Dec;13(12):1097–101.CrossRefPubMedGoogle Scholar
  12. 12.
    Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003 Sep 25;425(6956):415–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Morlando M, Ballarino M, Gromak N, Pagano F, Bozzoni I, Proudfoot NJ. Primary microRNA transcripts are processed co-transcriptionally. Nat Struct Mol Biol. 2008 Sep;15(9):902–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Li X, Carthew RW. A microRNA mediates EGF receptor signaling and promotes photoreceptor differentiation in the Drosophila eye. Cell. 2005 Dec 29;123(7):1267–77.CrossRefPubMedGoogle Scholar
  15. 15.
    Seggerson K, Tang L, Moss EG. Two genetic circuits repress the Caenorhabditis elegans heterochronic gene lin-28 after translation initiation. Dev Biol. 2002 Mar 15;243(2):215–25.CrossRefPubMedGoogle Scholar
  16. 16.
    Tay Y, Zhang J, Thomson AM, Lim B, Rigoutsos I. MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature. 2008 Oct 23;455(7216):1124–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, et al. Combinatorial microRNA target predictions. Nat Genet. 2005 May;37(5):495–500.CrossRefPubMedGoogle Scholar
  18. 18.
    Smalheiser NR, Torvik VI. Complications in mammalian microRNA target prediction. Methods Mol Biol. 2006;342:115–27.PubMedGoogle Scholar
  19. 19.
    Wienholds E, Plasterk RH. MicroRNA function in animal development. FEBS Lett. 2005 Oct 31;579(26):5911–22.CrossRefPubMedGoogle Scholar
  20. 20.
    Stefani G, Slack FJ. Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol. 2008 Mar;9(3):219–30.CrossRefPubMedGoogle Scholar
  21. 21.
    Yekta S, Tabin CJ, Bartel DP. MicroRNAs in the Hox network: an apparent link to posterior prevalence. Nat Rev Genet. 2008 Oct;9(10):789–96.CrossRefPubMedGoogle Scholar
  22. 22.
    Gangaraju VK, Lin H. MicroRNAs: key regulators of stem cells. Nat Rev Mol Cell Biol. 2009 Feb;10(2):116–25.CrossRefPubMedGoogle Scholar
  23. 23.
    Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 2007 Dec 14;131(6):1109–23.CrossRefPubMedGoogle Scholar
  24. 24.
    Petrocca F, Lieberman J. Micromanagers of immune cell fate and function. Adv Immunol. 2009;102:227–44.CrossRefPubMedGoogle Scholar
  25. 25.
    Pfeffer S, Zavolan M, Grasser FA, Chien M, Russo JJ, Ju J, et al. Identification of virus-encoded microRNAs. Science. 2004 Apr 30;304(5671):734–6.CrossRefPubMedGoogle Scholar
  26. 26.
    Stern-Ginossar N, Elefant N, Zimmermann A, Wolf DG, Saleh N, Biton M, et al. Host immune system gene targeting by a viral miRNA. Science. 2007 Jul 20;317(5836):376–81.CrossRefPubMedGoogle Scholar
  27. 27.
    Gottwein E, Mukherjee N, Sachse C, Frenzel C, Majoros WH, Chi JT, et al. A viral microRNA functions as an orthologue of cellular miR-155. Nature. 2007 Dec 13;450(7172):1096–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Nair V, Zavolan M. Virus-encoded microRNAs: novel regulators of gene expression. Trends Microbiol. 2006 Apr;14(4):169–75.CrossRefPubMedGoogle Scholar
  29. 29.
    Sullivan CS, Grundhoff AT, Tevethia S, Pipas JM, Ganem D. SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells. Nature. 2005 Jun 2;435(7042):682–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Grey F, Meyers H, White EA, Spector DH, Nelson J. A human cytomegalovirus-encoded microRNA regulates expression of multiple viral genes involved in replication. PLoS Pathog. 2007 Nov;3(11):e163.CrossRefPubMedGoogle Scholar
  31. 31.
    Barth S, Pfuhl T, Mamiani A, Ehses C, Roemer K, Kremmer E, et al. Epstein-Barr virus-encoded microRNA miR-BART2 down-regulates the viral DNA polymerase BALF5. Nucleic Acids Res. 2008 Feb;36(2):666–75.CrossRefPubMedGoogle Scholar
  32. 32.
    Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15524–9.CrossRefPubMedGoogle Scholar
  33. 33.
    Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13944–9.CrossRefPubMedGoogle Scholar
  34. 34.
    Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005 Jun 9;435(7043):834–8.CrossRefPubMedGoogle Scholar
  35. 35.
    Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2257–61.CrossRefPubMedGoogle Scholar
  36. 36.
    Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005 Oct 27;353(17):1793–801.CrossRefPubMedGoogle Scholar
  37. 37.
    Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006 Mar;9(3):189–98.CrossRefPubMedGoogle Scholar
  38. 38.
    Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10513–8.CrossRefPubMedGoogle Scholar
  39. 39.
    Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2999–3004.CrossRefPubMedGoogle Scholar
  40. 40.
    Zhang L, Huang J, Yang N, Greshock J, Megraw MS, Giannakakis A, et al. microRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9136–41.CrossRefPubMedGoogle Scholar
  41. 41.
    Zhang L, Volinia S, Bonome T, Calin GA, Greshock J, Yang N, et al. Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc Natl Acad Sci U S A. 2008 May 13;105(19):7004–9.CrossRefPubMedGoogle Scholar
  42. 42.
    Raveche ES, Salerno E, Scaglione BJ, Manohar V, Abbasi F, Lin YC, et al. Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice. Blood. 2007 Jun 15;109(12):5079–86.CrossRefPubMedGoogle Scholar
  43. 43.
    Sethupathy P, Collins FS. MicroRNA target site polymorphisms and human disease. Trends Genet. 2008 Oct;24(10):489–97.CrossRefPubMedGoogle Scholar
  44. 44.
    Scott GK, Mattie MD, Berger CE, Benz SC, Benz CC. Rapid alteration of microRNA levels by histone deacetylase inhibition. Cancer Res. 2006 Feb 1;66(3):1277–81.CrossRefPubMedGoogle Scholar
  45. 45.
    Saito Y, Liang G, Egger G, Friedman JM, Chuang JC, Coetzee GA, et al. Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell. 2006 Jun;9(6):435–43.CrossRefPubMedGoogle Scholar
  46. 46.
    Merritt WM, Lin YG, Han LY, Kamat AA, Spannuth WA, Schmandt R, et al. Dicer, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med. 2008 Dec 18;359(25):2641–50.CrossRefPubMedGoogle Scholar
  47. 47.
    Karube Y, Tanaka H, Osada H, Tomida S, Tatematsu Y, Yanagisawa K, et al. Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci. 2005 Feb;96(2):111–5.CrossRefPubMedGoogle Scholar
  48. 48.
    Carmell MA, Xuan Z, Zhang MQ, Hannon GJ. The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. Genes Dev. 2002 Nov 1;16(21):2733–42.CrossRefPubMedGoogle Scholar
  49. 49.
    Luciano DJ, Mirsky H, Vendetti NJ, Maas S. RNA editing of a miRNA precursor. RNA. 2004 Aug;10(8):1174–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Kawahara Y, Zinshteyn B, Chendrimada TP, Shiekhattar R, Nishikura K. RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex. EMBO Rep. 2007 Aug;8(8):763–9.CrossRefPubMedGoogle Scholar
  51. 51.
    Hartner JC, Schmittwolf C, Kispert A, Muller AM, Higuchi M, Seeburg PH. Liver disintegration in the mouse embryo caused by deficiency in the RNA-editing enzyme ADAR1. J Biol Chem. 2004 Feb 6;279(6):4894–902.CrossRefPubMedGoogle Scholar
  52. 52.
    Wang Q, Khillan J, Gadue P, Nishikura K. Requirement of the RNA editing deaminase ADAR1 gene for embryonic erythropoiesis. Science. 2000 Dec 1;290(5497):1765–8.CrossRefPubMedGoogle Scholar
  53. 53.
    Feng Y, Sansam CL, Singh M, Emeson RB. Altered RNA editing in mice lacking ADAR2 autoregulation. Mol Cell Biol. 2006 Jan;26(2):480–8.CrossRefPubMedGoogle Scholar
  54. 54.
    Paz N, Levanon EY, Amariglio N, Heimberger AB, Ram Z, Constantini S, et al. Altered adenosine-to-inosine RNA editing in human cancer. Genome Res. 2007 Nov;17(11):1586–95.CrossRefPubMedGoogle Scholar
  55. 55.
    Costinean S, Zanesi N, Pekarsky Y, Tili E, Volinia S, Heerema N, et al. Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice. Proc Natl Acad Sci U S A. 2006 May 2;103(18):7024–9.CrossRefPubMedGoogle Scholar
  56. 56.
    Eis PS, Tam W, Sun L, Chadburn A, Li Z, Gomez MF, et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3627–32.CrossRefPubMedGoogle Scholar
  57. 57.
    He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, et al. A microRNA polycistron as a potential human oncogene. Nature. 2005 Jun 9;435(7043):828–33.CrossRefPubMedGoogle Scholar
  58. 58.
    O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 2005 Jun 9;435(7043):839–43.CrossRefPubMedGoogle Scholar
  59. 59.
    Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005 Jul 15;65(14):6029–33.CrossRefPubMedGoogle Scholar
  60. 60.
    Krichevsky AM, Gabriely G. miR-21: a small multi-faceted RNA. J Cell Mol Med. 2009 Jan;13(1):39–53.CrossRefPubMedGoogle Scholar
  61. 61.
    Voorhoeve PM, le Sage C, Schrier M, Gillis AJ, Stoop H, Nagel R, et al. A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell. 2006 Mar 24;124(6):1169–81.CrossRefPubMedGoogle Scholar
  62. 62.
    Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, et al. RAS is regulated by the let-7 microRNA family. Cell. 2005 Mar 11;120(5):635–47.CrossRefPubMedGoogle Scholar
  63. 63.
    He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y, et al. A microRNA component of the p53 tumour suppressor network. Nature. 2007 Jun 28;447(7148):1130–4.CrossRefPubMedGoogle Scholar
  64. 64.
    Kumar MS, Erkeland SJ, Pester RE, Chen CY, Ebert MS, Sharp PA, et al. Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc Natl Acad Sci U S A. 2008 Feb 28.Google Scholar
  65. 65.
    Johnson CD, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D, et al. The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res. 2007 Aug 15;67(16):7713–22.CrossRefPubMedGoogle Scholar
  66. 66.
    Esquela-Kerscher A, Trang P, Wiggins JF, Patrawala L, Cheng A, Ford L, et al. The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle. 2008 Mar 3;7(6).Google Scholar
  67. 67.
    Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004 Jun 1;64(11):3753–6.CrossRefPubMedGoogle Scholar
  68. 68.
    Yang N, Kaur S, Volinia S, Greshock J, Lassus H, Hasegawa K, et al. MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer. Cancer Res. 2008 Dec 15;68(24):10307–14.CrossRefPubMedGoogle Scholar
  69. 69.
    Roush S, Slack FJ. The let-7 family of microRNAs. Trends Cell Biol. 2008 Oct;18(10):505–16.CrossRefPubMedGoogle Scholar
  70. 70.
    Bussing I, Slack FJ, Grosshans H. let-7 microRNAs in development, stem cells and cancer. Trends Mol Med. 2008 Jul 30.Google Scholar
  71. 71.
    Mayr C, Hemann MT, Bartel DP. Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science. 2007 Mar 16;315(5818):1576–9.CrossRefPubMedGoogle Scholar
  72. 72.
    Lee YS, Dutta A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev. 2007 May 1;21(9):1025–30.CrossRefPubMedGoogle Scholar
  73. 73.
    Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008 Oct;8(10):755–68.CrossRefPubMedGoogle Scholar
  74. 74.
    Nishino J, Kim I, Chada K, Morrison SJ. Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf Expression. Cell. 2008 Oct 17;135(2):227–39.CrossRefPubMedGoogle Scholar
  75. 75.
    Ibarra I, Erlich Y, Muthuswamy SK, Sachidanandam R, Hannon GJ. A role for microRNAs in maintenance of mouse mammary epithelial progenitor cells. Genes Dev. 2007 Dec 15;21(24):3238–43.CrossRefPubMedGoogle Scholar
  76. 76.
    Weiler J, Hunziker J, Hall J. Anti-miRNA oligonucleotides (AMOs): ammunition to target miRNAs implicated in human disease? Gene Ther. 2006 Mar;13(6):496–502.CrossRefPubMedGoogle Scholar
  77. 77.
    Elmen J, Lindow M, Schutz S, Lawrence M, Petri A, Obad S, et al. LNA-mediated microRNA silencing in non-human primates. Nature. 2008 Apr 17;452(7189):896–9.CrossRefPubMedGoogle Scholar
  78. 78.
    Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, et al. Silencing of microRNAs in vivo with ‘antagomirs’. Nature. 2005 Dec 1;438(7068):685–9.CrossRefPubMedGoogle Scholar
  79. 79.
    Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, et al. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006 Feb;3(2):87–98.CrossRefPubMedGoogle Scholar
  80. 80.
    Vermeulen A, Robertson B, Dalby AB, Marshall WS, Karpilow J, Leake D, et al. Double-stranded regions are essential design components of potent inhibitors of RISC function. RNA. 2007 May;13(5):723–30.CrossRefPubMedGoogle Scholar
  81. 81.
    Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY. miR-21-mediated tumor growth. Oncogene. 2007 Apr 26;26(19):2799–803.CrossRefPubMedGoogle Scholar
  82. 82.
    Corsten MF, Miranda R, Kasmieh R, Krichevsky AM, Weissleder R, Shah K. MicroRNA-21 knockdown disrupts glioma growth in vivo and displays synergistic cytotoxicity with neural precursor cell delivered S-TRAIL in human gliomas. Cancer Res. 2007 Oct 1;67(19):8994–9000.CrossRefPubMedGoogle Scholar
  83. 83.
    Ebert MS, Neilson JR, Sharp PA. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods. 2007 Sep;4(9):721–6.CrossRefPubMedGoogle Scholar
  84. 84.
    Xiao J, Yang B, Lin H, Lu Y, Luo X, Wang Z. Novel approaches for gene-specific interference via manipulating actions of microRNAs: examination on the pacemaker channel genes HCN2 and HCN4. J Cell Physiol. 2007 Aug;212(2):285–92.CrossRefPubMedGoogle Scholar
  85. 85.
    Choi WY, Giraldez AJ, Schier AF. Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430. Science. 2007 Oct 12;318(5848):271–4.CrossRefPubMedGoogle Scholar
  86. 86.
    Gumireddy K, Young DD, Xiong X, Hogenesch JB, Huang Q, Deiters A. Small-molecule inhibitors of microrna miR-21 function. Angew Chem Int Ed Engl. 2008;47(39):7482–4.CrossRefPubMedGoogle Scholar
  87. 87.
    Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, et al. The miR-15a-miR-16–1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 2008 Nov;14(11):1271–7.CrossRefPubMedGoogle Scholar
  88. 88.
    Kota J, Chivukula RR, O'Donnell KA, Wentzel EA, Montgomery CL, Hwang H-W, et al. Therapeutic microRNA Delivery Suppresses Tumorigenesis in a Murine Liver Cancer Model. Cell. 2009;137(6):1005–17.CrossRefPubMedGoogle Scholar
  89. 89.
    Landen CN Jr, Chavez-Reyes A, Bucana C, Schmandt R, Deavers MT, Lopez-Berestein G, et al. Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer Res. 2005 Aug 1;65(15):6910–8.CrossRefPubMedGoogle Scholar
  90. 90.
    Merritt WM, Lin YG, Spannuth WA, Fletcher MS, Kamat AA, Han LY, et al. Effect of interleukin-8 gene silencing with liposome-encapsulated small interfering RNA on ovarian cancer cell growth. J Natl Cancer Inst. 2008 Mar 5;100(5):359–72.CrossRefPubMedGoogle Scholar
  91. 91.
    Akinc A, Zumbuehl A, Goldberg M, Leshchiner ES, Busini V, Hossain N, et al. A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nat Biotechnol. 2008 May;26(5):561–9.CrossRefPubMedGoogle Scholar
  92. 92.
    Chiosea S, Jelezcova E, Chandran U, Luo J, Mantha G, Sobol RW, et al. Overexpression of Dicer in precursor lesions of lung adenocarcinoma. Cancer Res. 2007 Mar 1;67(5):2345–50.CrossRefPubMedGoogle Scholar
  93. 93.
    Flavin RJ, Smyth PC, Finn SP, Laios A, O'Toole SA, Barrett C, et al. Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients. Mod Pathol. 2008 Jun;21(6):676–84.CrossRefPubMedGoogle Scholar
  94. 94.
    Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet. 2007 May;39(5):673–7.CrossRefPubMedGoogle Scholar
  95. 95.
    Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, Davis CR, et al. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature. 2006 May 25;441(7092):537–41.CrossRefPubMedGoogle Scholar
  96. 96.
    Zhou R, Norton JE, Zhang N, Dean DA. Electroporation-mediated transfer of plasmids to the lung results in reduced TLR9 signaling and inflammation. Gene Ther. 2007 May;14(9):775–80.CrossRefPubMedGoogle Scholar
  97. 97.
    Judge AD, Sood V, Shaw JR, Fang D, McClintock K, MacLachlan I. Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA. Nat Biotechnol. 2005 Apr;23(4):457–62.CrossRefPubMedGoogle Scholar
  98. 98.
    Epanchintsev A, Jung P, Menssen A, Hermeking H. Inducible microRNA expression by an all-in-one episomal vector system. Nucleic Acids Res. 2006;34(18):e119.CrossRefPubMedGoogle Scholar
  99. 99.
    Snove O Jr, Rossi JJ. Toxicity in mice expressing short hairpin RNAs gives new insight into RNAi. Genome Biol. 2006;7(8):231.PubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2009

Authors and Affiliations

  • Chunsheng Li
    • 1
  • Yi Feng
    • 3
  • George Coukos
    • 1
    • 2
    • 3
  • Lin Zhang
    • 1
    • 2
    • 4
  1. 1.Center for Research on Early Detection and Cure of Ovarian CancerUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  2. 2.Department of Obstetrics and GynecologyUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  3. 3.Abramson Family Cancer Research InstituteUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  4. 4.University of Pennsylvania School of MedicinePhiladelphiaUSA

Personalised recommendations