Skip to main content

Advertisement

SpringerLink
Log in

microRNA Replacement Therapy for Cancer

  • Expert Review
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

ABSTRACT

microRNA are small noncoding RNAs that translationally repress their target messenger RNAs. Many microRNAs are expressed at reduced levels in tumors. microRNAs with reduced expression in cancer often regulate oncogenes, resulting in enhanced tumor growth. One therapeutic option is to restore microRNA levels in the tumor to that of the non-diseased tissue. This is possible by delivering microRNA to the tumor in the form of an oligonucleotide mimic or by expressing the microRNA in the cancer using a gene vector. This article surveys the field of oligonucleotide mimics and gene vector approaches to restore microRNA levels in tumors and reviews the literature on experimental and pre-clinical studies that have used these approaches to treat cancer.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

REFERENCES

  1. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.

    Article  PubMed  CAS  Google Scholar 

  2. Garzon R, Marcucci G, Croce CM. Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov. 2010;9(10):775–89.

    Article  PubMed  CAS  Google Scholar 

  3. Williams AH, Liu N, van Rooij E, Olson EN. MicroRNA control of muscle development and disease. Curr Opin Cell Biol. 2009;21(3):461–9.

    Article  PubMed  CAS  Google Scholar 

  4. Miller BH, Wahlestedt C. MicroRNA dysregulation in psychiatric disease. Brain Res. 2010;1338:89–99.

    Article  PubMed  CAS  Google Scholar 

  5. Guay C, Roggli E, Nesca V, Jacovetti C, Regazzi R. Diabetes mellitus, a microRNA-related disease? Transl Res. 2011;157(4):253–64.

    Article  PubMed  CAS  Google Scholar 

  6. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.

    Article  PubMed  CAS  Google Scholar 

  7. Krutzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, et al. Silencing of microRNAs in vivo with ‘antagomirs’. Nature. 2005;438(7068):685–9.

    Article  PubMed  CAS  Google Scholar 

  8. Bushati N, Cohen SM. MicroRNA functions. Annu Rev Cell Dev Biol. 2007;23:175–205.

    Article  PubMed  CAS  Google Scholar 

  9. Bartels CL, Tsongalis GJ. MicroRNAs: novel biomarkers for human cancer. Clin Chem. 2009;55(4):623–31.

    Article  PubMed  CAS  Google Scholar 

  10. Deiters A. Small molecule modifiers of the microRNA and RNA interference pathway. AAPS J. 2010;12(1):51–60.

    Article  PubMed  CAS  Google Scholar 

  11. Kim VN, Nam JW. Genomics of microRNA. Trends Genet. 2006;22(3):165–73.

    Article  PubMed  CAS  Google Scholar 

  12. Schwarz DS, Hutvagner G, Du T, Xu Z, Aronin N, Zamore PD. Asymmetry in the assembly of the RNAi enzyme complex. Cell. 2003;115(2):199–208.

    Article  PubMed  CAS  Google Scholar 

  13. Tolia NH, Joshua-Tor L. Slicer and the argonautes. Nat Chem Biol. 2007;3(1):36–43.

    Article  PubMed  CAS  Google Scholar 

  14. Lee I, Ajay SS, Yook JI, Kim HS, Hong SH, Kim NH, et al. New class of microRNA targets containing simultaneous 5′-UTR and 3′-UTR interaction sites. Genome Res. 2009;19(7):1175–83.

    Article  PubMed  CAS  Google Scholar 

  15. Lytle JR, Yario TA, Steitz JA. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR. Proc Natl Acad Sci U S A. 2007;104(23):9667–72.

    Article  PubMed  CAS  Google Scholar 

  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;455(7216):1124–8.

    Article  PubMed  CAS  Google Scholar 

  17. Calin GA, Liu CG, Ferracin M, Hyslop T, Spizzo R, Sevignani C, et al. Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell. 2007;12(3):215–29.

    Article  PubMed  CAS  Google Scholar 

  18. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–8.

    Article  PubMed  CAS  Google Scholar 

  19. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65(16):7065–70.

    Article  PubMed  CAS  Google Scholar 

  20. Jiang J, Gusev Y, Aderca I, Mettler TA, Nagorney DM, Brackett DJ, et al. Association of MicroRNA expression in hepatocellular carcinomas with hepatitis infection, cirrhosis, and patient survival. Clin Cancer Res. 2008;14(2):419–27.

    Article  PubMed  CAS  Google Scholar 

  21. Schmittgen TD, Jiang J, Liu Q, Yang L. A high-throughput method to monitor the expression of microRNA precursors. Nucleic Acids Res. 2004;32(4):E43.

    Article  PubMed  CAS  Google Scholar 

  22. 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;103(7):2257–61.

    Article  PubMed  CAS  Google Scholar 

  23. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65(16):7065–70.

    Article  PubMed  CAS  Google Scholar 

  24. Lee EJ, Gusev Y, Jiang J, Nuovo GJ, Lerner MR, Frankel WL, et al. Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer. 2007;120(5):1046–54.

    Article  PubMed  CAS  Google Scholar 

  25. 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;102(39):13944–9.

    Article  PubMed  CAS  Google Scholar 

  26. Meng F, Henson R, Lang M, Wehbe H, Maheshwari S, Mendell JT, et al. Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology. 2006;130(7):2113–29.

    Article  PubMed  CAS  Google Scholar 

  27. Wong P, Iwasaki M, Somervaille TC, Ficara F, Carico C, Arnold C, et al. The miR-17-92 microRNA polycistron regulates MLL leukemia stem cell potential by modulating p21 expression. Cancer Res. 2010;70(9):3833–42.

    Article  PubMed  CAS  Google Scholar 

  28. Fornari F, Gramantieri L, Ferracin M, Veronese A, Sabbioni S, Calin GA, et al. MiR-221 controls CDKN1C/p57 and CDKN1B/p27 expression in human hepatocellular carcinoma. Oncogene 2008.

  29. 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;101(9):2999–3004.

    Article  PubMed  CAS  Google Scholar 

  30. 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;9(6):435–43.

    Article  PubMed  CAS  Google Scholar 

  31. Melo SA, Moutinho C, Ropero S, Calin GA, Rossi S, Spizzo R, et al. A genetic defect in exportin-5 traps precursor microRNAs in the nucleus of cancer cells. Cancer Cell. 2010;18(4):303–15.

    Article  PubMed  CAS  Google Scholar 

  32. Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet. 2007;39(5):673–7.

    Article  PubMed  CAS  Google Scholar 

  33. 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;435(7043):828–33.

    Article  PubMed  CAS  Google Scholar 

  34. Medina PP, Nolde M, Slack FJ. OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature. 2010;467(7311):86–90.

    Article  PubMed  CAS  Google Scholar 

  35. 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;103(18):7024–9.

    Article  PubMed  CAS  Google Scholar 

  36. Pineau P, Volinia S, McJunkin K, Marchio A, Battiston C, Terris B, et al. MiR-221 over-expression contributes to liver tumorigenesis. Proc Natl Acad Sci U S A 2009.

  37. Wang B, Hsu SH, Majumder S, Kutay H, Huang W, Jacob ST, et al. TGFbeta-mediated upregulation of hepatic miR-181b promotes hepatocarcinogenesis by targeting TIMP3. Oncogene 2009.

  38. Papagiannakopoulos T, Shapiro A, Kosik KS. MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res. 2008;68(19):8164–72.

    Article  PubMed  CAS  Google Scholar 

  39. Wienholds E, Kloosterman WP, Miska E, Alvarez-Saavedra E, Berezikov E, de Bruijn E, et al. MicroRNA expression in zebrafish embryonic development. Science. 2005;309(5732):310–1.

    Article  PubMed  CAS  Google Scholar 

  40. Tsai WC, Hsu PW, Lai TC, Chau GY, Lin CW, Chen CM, et al. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology. 2009;49(5):1571–82.

    Article  PubMed  CAS  Google Scholar 

  41. Silber J, Lim DA, Petritsch C, Persson AI, Maunakea AK, Yu M, et al. MiR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Med. 2008;6:14.

    Article  PubMed  CAS  Google Scholar 

  42. Taulli R, Bersani F, Foglizzo V, Linari A, Vigna E, Ladanyi M, et al. The muscle-specific microRNA miR-206 blocks human rhabdomyosarcoma growth in xenotransplanted mice by promoting myogenic differentiation. J Clin Invest. 2009;119(8):2366–78.

    PubMed  CAS  Google Scholar 

  43. Silber J, Lim DA, Petritsch C, Persson AI, Maunakea AK, Yu M, et al. MiR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Med. 2008;6:14.

    Article  PubMed  CAS  Google Scholar 

  44. Behlke MA. Chemical modification of siRNAs for in vivo use. Oligonucleotides. 2008;18(4):305–19.

    Article  PubMed  CAS  Google Scholar 

  45. Amarzguioui M, Holen T, Babaie E, Prydz H. Tolerance for mutations and chemical modifications in a siRNA. Nucleic Acids Res. 2003;31(2):589–95.

    Article  PubMed  CAS  Google Scholar 

  46. Chiu YL, Rana TM. siRNA function in RNAi: a chemical modification analysis. RNA. 2003;9(9):1034–48.

    Article  PubMed  CAS  Google Scholar 

  47. Czauderna F, Fechtner M, Dames S, Aygun H, Klippel A, Pronk GJ, et al. Structural variations and stabilising modifications of synthetic siRNAs in mammalian cells. Nucleic Acids Res. 2003;31(11):2705–16.

    Article  PubMed  CAS  Google Scholar 

  48. Harborth J, Elbashir SM, Vandenburgh K, Manninga H, Scaringe SA, Weber K, et al. Sequence, chemical, and structural variation of small interfering RNAs and short hairpin RNAs and the effect on mammalian gene silencing. Antisense Nucleic Acid Drug Dev. 2003;13(2):83–105.

    Article  PubMed  CAS  Google Scholar 

  49. Choung S, Kim YJ, Kim S, Park HO, Choi YC. Chemical modification of siRNAs to improve serum stability without loss of efficacy. Biochem Biophys Res Commun. 2006;342(3):919–27.

    Article  PubMed  CAS  Google Scholar 

  50. Prakash TP, Allerson CR, Dande P, Vickers TA, Sioufi N, Jarres R, et al. Positional effect of chemical modifications on short interference RNA activity in mammalian cells. J Med Chem. 2005;48(13):4247–53.

    Article  PubMed  CAS  Google Scholar 

  51. Layzer JM, McCaffrey AP, Tanner AK, Huang Z, Kay MA, Sullenger BA. In vivo activity of nuclease-resistant siRNAs. RNA. 2004;10(5):766–71.

    Article  PubMed  CAS  Google Scholar 

  52. Morrissey DV, Lockridge JA, Shaw L, Blanchard K, Jensen K, Breen W, et al. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat Biotechnol. 2005;23(8):1002–7.

    Article  PubMed  CAS  Google Scholar 

  53. Kitade Y, Akao Y. MicroRNAs and their therapeutic potential for human diseases: microRNAs, miR-143 and −145, function as anti-oncomirs and the application of chemically modified miR-143 as an anti-cancer drug. J Pharmacol Sci. 2010;114(3):276–80.

    Article  PubMed  CAS  Google Scholar 

  54. Hamm S, Latz E, Hangel D, Muller T, Yu P, Golenbock D, et al. Alternating 2′-O-ribose methylation is a universal approach for generating non-stimulatory siRNA by acting as TLR7 antagonist. Immunobiology. 2010;215(7):559–69.

    Article  PubMed  CAS  Google Scholar 

  55. Eberle F, Giessler K, Deck C, Heeg K, Peter M, Richert C, et al. Modifications in small interfering RNA that separate immunostimulation from RNA interference. J Immunol. 2008;180(5):3229–37.

    PubMed  CAS  Google Scholar 

  56. Sioud M, Furset G, Cekaite L. Suppression of immunostimulatory siRNA-driven innate immune activation by 2′-modified RNAs. Biochem Biophys Res Commun. 2007;361(1):122–6.

    Article  PubMed  CAS  Google Scholar 

  57. Henry JC, Park JK, Jiang J, Kim JH, Nagorney DM, Roberts LR, et al. MiR-199a-3p targets CD44 and reduces proliferation of CD44 positive hepatocellular carcinoma cell lines. Biochem Biophys Res Commun. 2010;403(1):120–5.

    Article  PubMed  CAS  Google Scholar 

  58. 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;120(5):635–47.

    Article  PubMed  CAS  Google Scholar 

  59. Adhikary S, Eilers M. Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol. 2005;6(8):635–45.

    Article  PubMed  CAS  Google Scholar 

  60. Torrisani J, Bournet B, du Rieu MC, Bouisson M, Souque A, Escourrou J, et al. let-7 MicroRNA transfer in pancreatic cancer-derived cells inhibits in vitro cell proliferation but fails to alter tumor progression. Hum Gene Ther. 2009;20(8):831–44.

    Article  PubMed  CAS  Google Scholar 

  61. Long XB, Sun GB, Hu S, Liang GT, Wang N, Zhang XH, et al. Let-7a microRNA functions as a potential tumor suppressor in human laryngeal cancer. Oncol Rep. 2009;22(5):1189–95.

    PubMed  CAS  Google Scholar 

  62. Akao Y, Nakagawa Y, Naoe T. let-7 microRNA functions as a potential growth suppressor in human colon cancer cells. Biol Pharm Bull. 2006;29(5):903–6.

    Article  PubMed  CAS  Google Scholar 

  63. Lee YS, Dutta A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev. 2007;21(9):1025–30.

    Article  PubMed  CAS  Google Scholar 

  64. Sampson VB, Rong NH, Han J, Yang Q, Aris V, Soteropoulos P, et al. MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res. 2007;67(20):9762–70.

    Article  PubMed  CAS  Google Scholar 

  65. Lan FF, Wang H, Chen YC, Chan CY, Ng SS, Li K, et al. Hsa-let-7g inhibits proliferation of hepatocellular carcinoma cells by downregulation of c-Myc and upregulation of p16(INK4A). Int J Cancer. 2011;128(2):319–31.

    Article  PubMed  CAS  Google Scholar 

  66. Trang P, Wiggins JF, Daige CL, Cho C, Omotola M, Brown D, et al. Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice. Mol Ther 2011 Mar 22.

  67. Xiong Y, Fang JH, Yun JP, Yang J, Zhang Y, Jia WH, et al. Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology. 2010;51(3):836–45.

    PubMed  CAS  Google Scholar 

  68. Garzon R, Heaphy CE, Havelange V, Fabbri M, Volinia S, Tsao T, et al. MicroRNA 29b functions in acute myeloid leukemia. Blood. 2009;114(26):5331–41.

    Article  PubMed  CAS  Google Scholar 

  69. Su H, Yang JR, Xu T, Huang J, Xu L, Yuan Y, et al. MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Res. 2009;69(3):1135–42.

    Article  PubMed  CAS  Google Scholar 

  70. Ji Q, Hao X, Meng Y, Zhang M, Desano J, Fan D, et al. Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres. BMC Cancer. 2008;8:266.

    Article  PubMed  CAS  Google Scholar 

  71. Ji Q, Hao X, Zhang M, Tang W, Yang M, Li L, et al. MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PLoS One. 2009;4(8):e6816.

    Article  PubMed  CAS  Google Scholar 

  72. Kojima K, Fujita Y, Nozawa Y, Deguchi T, Ito M. MiR-34a attenuates paclitaxel-resistance of hormone-refractory prostate cancer PC3 cells through direct and indirect mechanisms. Prostate. 2010;70(14):1501–12.

    Article  PubMed  CAS  Google Scholar 

  73. Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, et al. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 2011;17(2):211–5.

    Article  PubMed  CAS  Google Scholar 

  74. Wiggins JF, Ruffino L, Kelnar K, Omotola M, Patrawala L, Brown D, et al. Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res. 2010;70(14):5923–30.

    Article  PubMed  CAS  Google Scholar 

  75. Tarasov V, Jung P, Verdoodt B, Lodygin D, Epanchintsev A, Menssen A, et al. 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. 2007;6(13):1586–93.

    Article  PubMed  CAS  Google Scholar 

  76. Bommer GT, Gerin I, Feng Y, Kaczorowski AJ, Kuick R, Love RE, et al. p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol. 2007;17(15):1298–307.

    Article  PubMed  CAS  Google Scholar 

  77. Yamakuchi M, Ferlito M, Lowenstein CJ. MiR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci U S A. 2008;105(36):13421–6.

    Article  PubMed  CAS  Google Scholar 

  78. Ji Q, Hao X, Meng Y, Zhang M, Desano J, Fan D, et al. Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres. BMC Cancer. 2008;8:266.

    Article  PubMed  CAS  Google Scholar 

  79. Wiggins JF, Ruffino L, Kelnar K, Omotola M, Patrawala L, Brown D, et al. Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res. 2010;70(14):5923–30.

    Article  PubMed  CAS  Google Scholar 

  80. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294(5543):853–8.

    Article  PubMed  CAS  Google Scholar 

  81. Chang J, Guo JT, Jiang D, Guo H, Taylor JM, Block TM. Liver-specific microRNA miR-122 enhances the replication of hepatitis C virus in nonhepatic cells. J Virol. 2008;82(16):8215–23.

    Article  PubMed  CAS  Google Scholar 

  82. Kutay H, Bai S, Datta J, Motiwala T, Pogribny I, Frankel W, et al. Downregulation of miR-122 in the rodent and human hepatocellular carcinomas. J Cell Biochem. 2006;99(3):671–8.

    Article  PubMed  CAS  Google Scholar 

  83. Hou J, Lin L, Zhou W, Wang Z, Ding G, Dong Q, et al. Identification of miRNomes in human liver and hepatocellular carcinoma reveals miR-199a/b-3p as therapeutic target for hepatocellular carcinoma. Cancer Cell. 2011;19(2):232–43.

    Article  PubMed  CAS  Google Scholar 

  84. Bai S, Nasser MW, Wang B, Hsu SH, Datta J, Kutay H, et al. MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J Biol Chem. 2009;284(46):32015–27.

    Article  PubMed  CAS  Google Scholar 

  85. Bai S, Nasser MW, Wang B, Hsu SH, Datta J, Kutay H, et al. MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J Biol Chem. 2009;284(46):32015–27.

    Article  PubMed  CAS  Google Scholar 

  86. Akao Y, Nakagawa Y, Naoe T. MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncol Rep. 2006;16(4):845–50.

    PubMed  CAS  Google Scholar 

  87. Akao Y, Nakagawa Y, Naoe T. MicroRNA-143 and −145 in colon cancer. DNA Cell Biol. 2007;26(5):311–20.

    Article  PubMed  CAS  Google Scholar 

  88. Zhang J, Guo H, Zhang H, Wang H, Qian G, Fan X, et al. Putative tumor suppressor miR-145 inhibits colon cancer cell growth by targeting oncogene Friend leukemia virus integration 1 gene. Cancer. 2011;117(1):86–95.

    Article  PubMed  CAS  Google Scholar 

  89. Gregersen LH, Jacobsen AB, Frankel LB, Wen J, Krogh A, Lund AH. MicroRNA-145 targets YES and STAT1 in colon cancer cells. PLoS One. 2010;5(1):e8836.

    Article  PubMed  CAS  Google Scholar 

  90. Esau C, Kang X, Peralta E, Hanson E, Marcusson EG, Ravichandran LV, et al. MicroRNA-143 regulates adipocyte differentiation. J Biol Chem. 2004;279(50):52361–5.

    Article  PubMed  CAS  Google Scholar 

  91. Fornari F, Milazzo M, Chieco P, Negrini M, Calin GA, Grazi GL, et al. MiR-199a-3p regulates mTOR and c-Met to influence the doxorubicin sensitivity of human hepatocarcinoma cells. Cancer Res. 2010;70(12):5184–93.

    Article  PubMed  CAS  Google Scholar 

  92. Gramantieri L, Ferracin M, Fornari F, Veronese A, Sabbioni S, Liu CG, et al. Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res. 2007;67(13):6092–9.

    Article  PubMed  CAS  Google Scholar 

  93. Henry JC, Park JK, Jiang J, Kim JH, Nagorney DM, Roberts LR, et al. MiR-199a-3p targets CD44 and reduces proliferation of CD44 positive hepatocellular carcinoma cell lines. Biochem Biophys Res Commun. 2010;403(1):120–5.

    Article  PubMed  CAS  Google Scholar 

  94. Kim S, Lee UJ, Kim MN, Lee EJ, Kim JY, Lee MY, et al. MicroRNA miR-199a* regulates the MET proto-oncogene and the downstream extracellular signal-regulated kinase 2 (ERK2). J Biol Chem. 2008;283(26):18158–66.

    Article  PubMed  CAS  Google Scholar 

  95. Murakami Y, Aly HH, Tajima A, Inoue I, Shimotohno K. Regulation of the hepatitis C virus genome replication by miR-199a. J Hepatol. 2009;50(3):453–60.

    Article  PubMed  CAS  Google Scholar 

  96. Bo J, Yang G, Huo K, Jiang H, Zhang L, Liu D, et al. MicroRNA-203 suppresses bladder cancer development by repressing bcl-w expression. FEBS J. 2011;278(5):786–92.

    Article  PubMed  CAS  Google Scholar 

  97. Gottardo F, Liu CG, Ferracin M, Calin GA, Fassan M, Bassi P, et al. Micro-RNA profiling in kidney and bladder cancers. Urol Oncol. 2007;25(5):387–92.

    Article  PubMed  CAS  Google Scholar 

  98. Castilla MA, Moreno-Bueno G, Romero-Perez L, Van De Vijver K, Biscuola M, Lopez-Garcia MA, et al. Micro-RNA signature of the epithelial-mesenchymal transition in endometrial carcinosarcoma. J Pathol. 2011;223(1):72–80.

    Article  PubMed  CAS  Google Scholar 

  99. Chiang Y, Song Y, Wang Z, Chen Y, Yue Z, Xu H, et al. Aberrant expression of miR-203 and its clinical significance in gastric and colorectal cancers. J Gastrointest Surg. 2011;15(1):63–70.

    Article  PubMed  Google Scholar 

  100. Zhu H, Wu H, Liu X, Evans BR, Medina DJ, Liu CG, et al. Role of MicroRNA miR-27a and miR-451 in the regulation of MDR1/P-glycoprotein expression in human cancer cells. Biochem Pharmacol. 2008;76(5):582–8.

    Article  PubMed  CAS  Google Scholar 

  101. Liang Z, Wu H, Xia J, Li Y, Zhang Y, Huang K, et al. Involvement of miR-326 in chemotherapy resistance of breast cancer through modulating expression of multidrug resistance-associated protein 1. Biochem Pharmacol. 2010;79(6):817–24.

    Article  PubMed  CAS  Google Scholar 

  102. Kovalchuk O, Filkowski J, Meservy J, Ilnytskyy Y, Tryndyak VP, Chekhun VF, et al. Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin. Mol Cancer Ther. 2008;7(7):2152–9.

    Article  PubMed  CAS  Google Scholar 

  103. Noonan EJ, Place RF, Basak S, Pookot D, Li LC. MiR-449a causes Rb-dependent cell cycle arrest and senescence in prostate cancer cells. Oncotarget. 2010;1(5):349–58.

    PubMed  Google Scholar 

  104. Noonan EJ, Place RF, Pookot D, Basak S, Whitson JM, Hirata H, et al. MiR-449a targets HDAC-1 and induces growth arrest in prostate cancer. Oncogene. 2009;28(14):1714–24.

    Article  PubMed  CAS  Google Scholar 

  105. Nan Y, Han L, Zhang A, Wang G, Jia Z, Yang Y, et al. miRNA-451 plays a role as tumor suppressor in human glioma cells. Brain Res. 2010;1359:14–21.

    Article  PubMed  CAS  Google Scholar 

  106. Wang F, Xue X, Wei J, An Y, Yao J, Cai H, et al. hsa-miR-520h downregulates ABCG2 in pancreatic cancer cells to inhibit migration, invasion, and side populations. Br J Cancer. 2010;103(4):567–74.

    Article  PubMed  CAS  Google Scholar 

  107. Tsuda N, Kawano K, Efferson CL, Ioannides CG. Synthetic microRNA and double-stranded RNA targeting the 3′-untranslated region of HER-2/neu mRNA inhibit HER-2 protein expression in ovarian cancer cells. Int J Oncol. 2005;27(5):1299–306.

    PubMed  CAS  Google Scholar 

  108. Tsuda N, Ishiyama S, Li Y, Ioannides CG, Abbruzzese JL, Chang DZ. Synthetic microRNA designed to target glioma-associated antigen 1 transcription factor inhibits division and induces late apoptosis in pancreatic tumor cells. Clin Cancer Res. 2006;12(21):6557–64.

    Article  PubMed  CAS  Google Scholar 

  109. Sibley CR, Seow Y, Wood MJ. Novel RNA-based strategies for therapeutic gene silencing. Mol Ther. 2010;18(3):466–76.

    Article  PubMed  CAS  Google Scholar 

  110. Godlewski J, Nowicki MO, Bronisz A, Williams S, Otsuki A, Nuovo G, et al. Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. Cancer Res. 2008;68(22):9125–30.

    Article  PubMed  CAS  Google Scholar 

  111. Sachdeva M, Zhu S, Wu F, Wu H, Walia V, Kumar S, et al. p53 represses c-Myc through induction of the tumor suppressor miR-145. Proc Natl Acad Sci U S A. 2009;106(9):3207–12.

    Article  PubMed  CAS  Google Scholar 

  112. Chen Z, Zeng H, Guo Y, Liu P, Pan H, Deng A, et al. miRNA-145 inhibits non-small cell lung cancer cell proliferation by targeting c-Myc. J Exp Clin Cancer Res. 2010;29:151.

    Article  PubMed  CAS  Google Scholar 

  113. Yan D, Dong Xda E, Chen X, Wang L, Lu C, Wang J, et al. MicroRNA-1/206 targets c-Met and inhibits rhabdomyosarcoma development. J Biol Chem. 2009;284(43):29596–604.

    Article  PubMed  CAS  Google Scholar 

  114. 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;7(6):759–64.

    Article  PubMed  CAS  Google Scholar 

  115. Trang P, Medina PP, Wiggins JF, Ruffino L, Kelnar K, Omotola M, et al. Regression of murine lung tumors by the let-7 microRNA. Oncogene. 2010;29(11):1580–7.

    Article  PubMed  CAS  Google Scholar 

  116. Sun Y, Bai Y, Zhang F, Wang Y, Guo Y, Guo L. MiR-126 inhibits non-small cell lung cancer cells proliferation by targeting EGFL7. Biochem Biophys Res Commun. 2010;391(3):1483–9.

    Article  PubMed  CAS  Google Scholar 

  117. Feng R, Chen X, Yu Y, Su L, Yu B, Li J, et al. MiR-126 functions as a tumour suppressor in human gastric cancer. Cancer Lett. 2010;298(1):50–63.

    Article  PubMed  CAS  Google Scholar 

  118. Bian HB, Pan X, Yang JS, Wang ZX, De W. Upregulation of microRNA-451 increases cisplatin sensitivity of non-small cell lung cancer cell line (A549). J Exp Clin Cancer Res. 2011;30:20.

    Article  PubMed  CAS  Google Scholar 

  119. Zhang X, Ladd A, Dragoescu E, Budd WT, Ware JL, Zehner ZE. MicroRNA-17-3p is a prostate tumor suppressor in vitro and in vivo, and is decreased in high grade prostate tumors analyzed by laser capture microdissection. Clin Exp Metastasis. 2009;26(8):965–79.

    Article  PubMed  CAS  Google Scholar 

  120. Dong Q, Meng P, Wang T, Qin W, Qin W, Wang F, et al. MicroRNA let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. PLoS One. 2010;5(4):e10147.

    Article  PubMed  CAS  Google Scholar 

  121. Yu S, Lu Z, Liu C, Meng Y, Ma Y, Zhao W, et al. miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer. Cancer Res. 2010;70(14):6015–25.

    Article  PubMed  CAS  Google Scholar 

  122. Dar AA, Majid S, de Semir D, Nosrati M, Bezrookove V, Kashani-Sabet M. MiR-205 suppresses melanoma cell proliferation and induces senescence via regulation of E2F1. J Biol Chem 2011 Mar 24.

  123. Kota SK, Balasubramanian S. Cancer therapy via modulation of micro RNA levels: a promising future. Drug Discov Today. 2010;15(17–18):733–40.

    Article  PubMed  CAS  Google Scholar 

  124. Wang HJ, Ruan HJ, He XJ, Ma YY, Jiang XT, Xia YJ, et al. MicroRNA-101 is down-regulated in gastric cancer and involved in cell migration and invasion. Eur J Cancer 2010 Jun 5.

  125. Viswanathan SR, Powers JT, Einhorn W, Hoshida Y, Ng TL, Toffanin S, et al. Lin28 promotes transformation and is associated with advanced human malignancies. Nat Genet. 2009;41(7):843–8.

    Article  PubMed  CAS  Google Scholar 

  126. Peacock H, Fucini RV, Jayalath P, Ibarra-Soza JM, Haringsma HJ, Flanagan WM, et al. Nucleobase and Ribose Modifications Control Immunostimulation by a MicroRNA-122-mimetic RNA. J Am Chem Soc 2011 Jun 1.

Download references

ACKNOWLEDGMENTS & DISCLOSURES

This work was funded by R33 CA114304 to T.D.S. J.C.H. is supported by NIH Training Grant 7T32 CA009338. A.C.P.A-P. is supported by NIH predoctoral fellowship F31 CA142238. We thank Dr. Mark Behlke of Integrated DNA technologies for the optimization of the miRNA mimic chemistry. We apologize to our colleagues whose work could not be cited here due to space limitations.

Author information

Authors and Affiliations

  1. College of Pharmacy, Ohio State University, Columbus, Ohio, USA

    Jon C. Henry, Ana Clara P. Azevedo-Pouly & Thomas D. Schmittgen

  2. Department of Surgery, Ohio State University, Columbus, Ohio, USA

    Jon C. Henry

Authors
  1. Jon C. Henry
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ana Clara P. Azevedo-Pouly
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Thomas D. Schmittgen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas D. Schmittgen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Henry, J.C., Azevedo-Pouly, A.C.P. & Schmittgen, T.D. microRNA Replacement Therapy for Cancer. Pharm Res 28, 3030–3042 (2011). https://doi.org/10.1007/s11095-011-0548-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-011-0548-9

KEY WORDS

Search

Navigation