Micrornas as molecular targets for cancer therapy: On the modulation of microrna expression

Pharmaceuticals

Volumn 6, Issue 10, 2013, Pages 1195-1220

  Costa, Pedro M ^a   De Lima, Maria C Pedroso ^b  

^a UNIVERSITY OF COIMBRA   (Portugal)

^b UNIVERSITY OF COIMBRA   (Portugal)

Author keywords

Anti mirna oligonucleotides; Cancer therapy; Microrna (mirna); miRNA mimics; Viral and non viral carriers

Indexed keywords

EID: 84885029680     PISSN: None     EISSN: 14248247     Source Type: Journal    
DOI: 10.3390/ph6101195     Document Type: Article

References (156)

1. Alvarez-Garcia, I.; Miska, E.A. Microrna functions in animal development and human disease. Development 2005, 132, 4653-4662.
2. Ambros, V. The functions of animal micrornas. Nature 2004, 431, 350-355.
3. Croce, C.M. Causes and consequences of microrna dysregulation in cancer. Nat. Rev. Genet. 2009, 10, 704-714.
4. Stark, A.; Brennecke, J.; Bushati, N.; Russell, R.B.; Cohen, S.M. Animal micrornas confer robustness to gene expression and have a significant impact on 3'Utr evolution. Cell 2005, 123, 1133-1146.
5. Liu, N.; Olson, E.N. Microrna regulatory networks in cardiovascular development. Dev. Cell 2010, 18, 510-525.
6. Gangaraju, V.K.; Lin, H. Micrornas: Key regulators of stem cells. Nat. Rev. Mol. Cell Biol. 2009, 10, 116-125.
7. O'Connell, R.M.; Rao, D.S.; Chaudhuri, A.A.; Baltimore, D. Physiological and pathological roles for micrornas in the immune system. Nat. Rev. Immunol. 2010, 10, 111-122.
8. Poy, M.N.; Eliasson, L.; Krutzfeldt, J.; Kuwajima, S.; Ma, X.; Macdonald, P.E.; Pfeffer, S.; Tuschl, T.; Rajewsky, N.; Rorsman, P. et al. A pancreatic islet-specific microrna regulates insulin secretion. Nature 2004, 432, 226-230.
9. Lecellier, C.H.; Dunoyer, P.; Arar, K.; Lehmann-Che, J.; Eyquem, S.; Himber, C.; Saib, A.; Voinnet, O. A cellular microrna mediates antiviral defense in human cells. Science 2005, 308, 557-560.
10. Nelson, P.T.; Wang, W.X.; Rajeev, B.W. Micrornas (mirnas) in neurodegenerative diseases. Brain Pathol. 2008, 18, 130-138.
11. Small, E.M.; Olson, E.N. Pervasive roles of micrornas in cardiovascular biology. Nature 2011, 469, 336-342.
12. Pandey, A.K.; Agarwal, P.; Kaur, K.; Datta, M. Micrornas in diabetes: Tiny players in big disease. Cell. Physiol. Biochem. 2009, 23, 221-232.
13. Calin, G.A.; Croce, C.M. Microrna signatures in human cancers. Nat. Rev. Cancer 2006, 6, 857-866.
14. Ruby, J.G.; Jan, C.H.; Bartel, D.P. Intronic microrna precursors that bypass drosha processing. Nature 2007, 448, 83-86.
15. Meister, G.; Landthaler, M.; Patkaniowska, A.; Dorsett, Y.; Teng, G.; Tuschl, T. Human argonaute2 mediates rna cleavage targeted by mirnas and sirnas. Mol. Cell 2004, 15, 185-197.
16. Filipowicz, W.; Bhattacharyya, S.N.; Sonenberg, N. Mechanisms of post-transcriptional regulation by micrornas: Are the answers in sight? Nat. Rev. Genet. 2008, 9, 102-114.
17. Perron, M.P.; Provost, P. Protein interactions and complexes in human microrna biogenesis and function. Front. Biosci. 2008, 13, 2537-2547.
18. Bartel, D.P. Micrornas: Genomics, biogenesis, mechanism, and function. Cell 2004, 116, 281-297.
19. Brennecke, J.; Stark, A.; Russell, R.B.; Cohen, S.M. Principles of microrna-target recognition. PLoS Biol. 2005, 3, e85.
20. Liu, X.; Fortin, K.; Mourelatos, Z. Micrornas: Biogenesis and molecular functions. Brain Pathol. 2008, 18, 113-121.
21. Kiriakidou, M.; Nelson, P.T.; Kouranov, A.; Fitziev, P.; Bouyioukos, C.; Mourelatos, Z.; Hatzigeorgiou, A. A combined computational-experimental approach predicts human microrna targets. Genes Dev. 2004, 18, 1165-1178.
22. Fabian, M.R.; Sonenberg, N. The mechanics of mirna-mediated gene silencing: A look under the hood of mirisc. Nat. Struct. Mol. Biol. 2012, 19, 586-593.
23. Chendrimada, T.P.; Finn, K.J.; Ji, X.; Baillat, D.; Gregory, R.I.; Liebhaber, S.A.; Pasquinelli, A.E.; Shiekhattar, R. Microrna silencing through risc recruitment of eif6. Nature 2007, 447, 823-828.
24. Fabian, M.R.; Mathonnet, G.; Sundermeier, T.; Mathys, H.; Zipprich, J.T.; Svitkin, Y.V.; Rivas, F.; Jinek, M.; Wohlschlegel, J.; Doudna, J.A. et al. Mammalian mirna risc recruits caf1 and pabp to affect pabp-dependent deadenylation. Mol. Cell 2009, 35, 868-880.
25. Baek, D.; Villen, J.; Shin, C.; Camargo, F.D.; Gygi, S.P.; Bartel, D.P. The impact of micrornas on protein output. Nature 2008, 455, 64-71.
26. Guo, H.; Ingolia, N.T.; Weissman, J.S.; Bartel, D.P. Mammalian micrornas predominantly act to decrease target mrna levels. Nature 2010, 466, 835-840.
27. Selbach, M.; Schwanhausser, B.; Thierfelder, N.; Fang, Z.; Khanin, R.; Rajewsky, N. Widespread changes in protein synthesis induced by micrornas. Nature 2008, 455, 58-63.
28. Behm-Ansmant, I.; Rehwinkel, J.; Doerks, T.; Stark, A.; Bork, P.; Izaurralde, E. Mrna degradation by mirnas and gw182 requires both ccr4:Not deadenylase and dcp1:Dcp2 decapping complexes. Genes Dev. 2006, 20, 1885-1898.
29. Giraldez, A.J.; Mishima, Y.; Rihel, J.; Grocock, R.J.; Van Dongen, S.; Inoue, K.; Enright, A.J.; Schier, A.F. Zebrafish mir-430 promotes deadenylation and clearance of maternal mrnas. Science 2006, 312, 75-79.
30. Wu, L.; Fan, J.; Belasco, J.G. Micrornas direct rapid deadenylation of mrna. Proc. Natl. Acad. Sci. USA 2006, 103, 4034-4039.
31. Calin, G.A.; Dumitru, C.D.; Shimizu, M.; Bichi, R.; Zupo, S.; Noch, E.; Aldler, H.; Rattan, S.; Keating, M.; Rai, K. et al. Frequent deletions and down-regulation of micro-rna genes mir15 and mir16 at 13q14 in chronic lymphocytic leukemia. Proc. Natl. Acad. Sci. USA 2002, 99, 15524-15529.
32. Calin, G.A.; Sevignani, C.; Dumitru, C.D.; Hyslop, T.; Noch, E.; Yendamuri, S.; Shimizu, M.; Rattan, S.; Bullrich, F.; Negrini, M. et al. Human microrna genes are frequently located at fragile sites and genomic regions involved in cancers. Proc. Natl. Acad. Sci. USA 2004, 101, 2999-3004.
33. Kumar, M.S.; Lu, J.; Mercer, K.L.; Golub, T.R.; Jacks, T. Impaired microrna processing enhances cellular transformation and tumorigenesis. Nat. Genet. 2007, 39, 673-677.
34. 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. et al. Microrna expression profiles classify human cancers. Nature 2005, 435, 834-838.
35. Volinia, S.; Calin, G.A.; Liu, C.G.; Ambs, S.; Cimmino, A.; Petrocca, F.; Visone, R.; Iorio, M.; Roldo, C.; Ferracin, M. et al. A microrna expression signature of human solid tumors defines cancer gene targets. Proc. Natl. Acad. Sci. USA 2006, 103, 2257-2261.
36. 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. et al. A microrna signature associated with prognosis and progression in chronic lymphocytic leukemia. N. Engl. J. Med. 2005, 353, 1793-1801.
37. Yanaihara, N.; Caplen, N.; Bowman, E.; Seike, M.; Kumamoto, K.; Yi, M.; Stephens, R.M.; Okamoto, A.; Yokota, J.; Tanaka, T. et al. Unique microrna molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 2006, 9, 189-198.
38. Esquela-Kerscher, A.; Slack, F.J. Oncomirs-Micrornas with a role in cancer. Nat. Rev. Cancer 2006, 6, 259-269.
39. Cimmino, A.; Calin, G.A.; Fabbri, M.; Iorio, M.V.; Ferracin, M.; Shimizu, M.; Wojcik, S.E.; Aqeilan, R.I.; Zupo, S.; Dono, M. et al. Mir-15 and mir-16 induce apoptosis by targeting bcl2. Proc. Natl. Acad. Sci. USA 2005, 102, 13944-13949.
40. Ambs, S.; Prueitt, R.L.; Yi, M.; Hudson, R.S.; Howe, T.M.; Petrocca, F.; Wallace, T.A.; Liu, C.G.; Volinia, S.; Calin, G.A. et al. Genomic profiling of microrna and messenger rna reveals deregulated microrna expression in prostate cancer. Cancer Res. 2008, 68, 6162-6170.
41. Roccaro, A.M.; Sacco, A.; Thompson, B.; Leleu, X.; Azab, A.K.; Azab, F.; Runnels, J.; Jia, X.; Ngo, H.T.; Melhem, M.R. et al. Micrornas 15a and 16 regulate tumor proliferation in multiple myeloma. Blood 2009, 113, 6669-6680.
42. 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, 903-906.
43. Iorio, M.V.; Ferracin, M.; Liu, C.G.; Veronese, A.; Spizzo, R.; Sabbioni, S.; Magri, E.; Pedriali, M.; Fabbri, M.; Campiglio, M. et al. Microrna gene expression deregulation in human breast cancer. Cancer Res. 2005, 65, 7065-7070.
44. Esquela-Kerscher, A.; Trang, P.; Wiggins, J.F.; Patrawala, L.; Cheng, A.; Ford, L.; Weidhaas, J.B.; Brown, D.; Bader, A.G.; Slack, F.J. The let-7 microrna reduces tumor growth in mouse models of lung cancer. Cell Cycle 2008, 7, 759-764.
45. Johnson, S.M.; Grosshans, H.; Shingara, J.; Byrom, M.; Jarvis, R.; Cheng, A.; Labourier, E.; Reinert, K.L.; Brown, D.; Slack, F.J. Ras is regulated by the let-7 microrna family. Cell 2005, 120, 635-647.
46. Lee, Y.S.; Dutta, A. The tumor suppressor microrna let-7 represses the hmga2 oncogene. Genes Dev. 2007, 21, 1025-1030.
47. Sampson, V.B.; Rong, N.H.; Han, J.; Yang, Q.; Aris, V.; Soteropoulos, P.; Petrelli, N.J.; Dunn, S.P.; Krueger, L.J. Microrna let-7a down-regulates myc and reverts myc-induced growth in burkitt lymphoma cells. Cancer Res. 2007, 67, 9762-9770.
48. Xiong, Y.; Fang, J.H.; Yun, J.P.; Yang, J.; Zhang, Y.; Jia, W.H.; Zhuang, S.M. Effects of microrna-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology 2010, 51, 836-845.
49. Fabbri, M.; Garzon, R.; Cimmino, A.; Liu, Z.; Zanesi, N.; Callegari, E.; Liu, S.; Alder, H.; Costinean, S.; Fernandez-Cymering, C. et al. Microrna-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3a and 3b. Proc. Natl. Acad. Sci. USA 2007, 104, 15805-15810.
50. Corney, D.C.; Hwang, C.I.; Matoso, A.; Vogt, M.; Flesken-Nikitin, A.; Godwin, A.K.; Kamat, A.A.; Sood, A.K.; Ellenson, L.H.; Hermeking, H. et al. Frequent downregulation of mir-34 family in human ovarian cancers. Clin. Cancer Res. 2010, 16, 1119-1128.
51. Fabbri, M.; Bottoni, A.; Shimizu, M.; Spizzo, R.; Nicoloso, M.S.; Rossi, S.; Barbarotto, E.; Cimmino, A.; Adair, B.; Wojcik, S.E. et al. Association of a microrna/tp53 feedback circuitry with pathogenesis and outcome of b-cell chronic lymphocytic leukemia. JAMA 2011, 305, 59-67.
52. Tanaka, N.; Toyooka, S.; Soh, J.; Kubo, T.; Yamamoto, H.; Maki, Y.; Muraoka, T.; Shien, K.; Furukawa, M.; Ueno, T. et al. Frequent methylation and oncogenic role of microrna-34b/c in small-cell lung cancer. Lung Cancer 2011, 76, 32-38.
53. Vogt, M.; Munding, J.; Gruner, M.; Liffers, S.T.; Verdoodt, B.; Hauk, J.; Steinstraesser, L.; Tannapfel, A.; Hermeking, H. Frequent concomitant inactivation of mir-34a and mir-34b/c by cpg methylation in colorectal, pancreatic, mammary, ovarian, urothelial, and renal cell carcinomas and soft tissue sarcomas. Virchows Arch. 2011, 458, 313-322.
54. Li, Y.; Guessous, F.; Zhang, Y.; Dipierro, C.; Kefas, B.; Johnson, E.; Marcinkiewicz, L.; Jiang, J.; Yang, Y.; Schmittgen, T.D. et al. Microrna-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res. 2009, 69, 7569-7576.
55. He, L.; He, X.; Lim, L.P.; de Stanchina, E.; Xuan, Z.; Liang, Y.; Xue, W.; Zender, L.; Magnus, J.; Ridzon, D. et al. A microrna component of the p53 tumour suppressor network. Nature 2007, 447, 1130-1134.
56. Rokhlin, O.W.; Scheinker, V.S.; Taghiyev, A.F.; Bumcrot, D.; Glover, R.A.; Cohen, M.B. Microrna-34 mediates ar-dependent p53-induced apoptosis in prostate cancer. Cancer Biol. Ther. 2008, 7, 1288-1296.
57. Garzon, R.; Calin, G.A.; Croce, C.M. Micrornas in cancer. Annu. Rev. Med. 2009, 60, 167-179.
58. 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. et al. A microrna polycistron as a potential human oncogene. Nature 2005, 435, 828-833.
59. Ota, A.; Tagawa, H.; Karnan, S.; Tsuzuki, S.; Karpas, A.; Kira, S.; Yoshida, Y.; Seto, M. Identification and characterization of a novel gene, c13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res. 2004, 64, 3087-3095.
60. Mendell, J.T. Miriad roles for the mir-17-92 cluster in development and disease. Cell 2008, 133, 217-222.
61. Dews, M.; Homayouni, A.; Yu, D.; Murphy, D.; Sevignani, C.; Wentzel, E.; Furth, E.E.; Lee, W.M.; Enders, G.H.; Mendell, J.T. et al. Augmentation of tumor angiogenesis by a myc-activated microrna cluster. Nat. Genet. 2006, 38, 1060-1065.
62. O'Donnell, K.A.; Wentzel, E.A.; Zeller, K.I.; Dang, C.V.; Mendell, J.T. C-myc-regulated micrornas modulate e2f1 expression. Nature 2005, 435, 839-843.
63. Ivanovska, I.; Ball, A.S.; Diaz, R.L.; Magnus, J.F.; Kibukawa, M.; Schelter, J.M.; Kobayashi, S.V.; Lim, L.; Burchard, J.; Jackson, A.L. et al. Micrornas in the mir-106b family regulate p21/cdkn1a and promote cell cycle progression. Mol. Cell. Biol. 2008, 28, 2167-2174.
64. Bloomston, M.; Frankel, W.L.; Petrocca, F.; Volinia, S.; Alder, H.; Hagan, J.P.; Liu, C.G.; Bhatt, D.; Taccioli, C.; Croce, C.M. Microrna expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA 2007, 297, 1901-1908.
65. Meng, F.; Henson, R.; Wehbe-Janek, H.; Ghoshal, K.; Jacob, S.T.; Patel, T. Microrna-21 regulates expression of the pten tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007, 133, 647-658.
66. Selcuklu, S.D.; Donoghue, M.T.; Spillane, C. Mir-21 as a key regulator of oncogenic processes. Biochem. Soc. Trans. 2009, 37, 918-925.
67. Novakova, J.; Slaby, O.; Vyzula, R.; Michalek, J. Microrna involvement in glioblastoma pathogenesis. Biochem. Biophys. Res. Commun. 2009, 386, 1-5.
68. Sana, J.; Hajduch, M.; Michalek, J.; Vyzula, R.; Slaby, O. Micrornas and glioblastoma: Roles in core signalling pathways and potential clinical implications. J. Cell. Mol. Med. 2011, 15, 1636-1644.
69. Zhang, Y.; Dutta, A.; Abounader, R. The role of micrornas in glioma initiation and progression. Front. Biosci. 2012, 17, 700-712.
70. Goke, R.; Barth, P.; Schmidt, A.; Samans, B.; Lankat-Buttgereit, B. Programmed cell death protein 4 suppresses cdk1/cdc2 via induction of p21(waf1/cip1). Am. J. Physiol. Cell. Physiol. 2004, 287, C1541-C1546.
71. Papagiannakopoulos, T.; Shapiro, A.; Kosik, K.S. Microrna-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. Cancer Res. 2008, 68, 8164-8172.
72. Gabriely, G.; Wurdinger, T.; Kesari, S.; Esau, C.C.; Burchard, J.; Linsley, P.S.; Krichevsky, A.M. Microrna 21 promotes glioma invasion by targeting matrix metalloproteinase regulators. Mol. Cell. Biol. 2008, 28, 5369-5380.
73. Gabriely, G.; Yi, M.; Narayan, R.S.; Niers, J.M.; Wurdinger, T.; Imitola, J.; Ligon, K.L.; Kesari, S.; Esau, C.; Stephens, R.M. et al. Human glioma growth is controlled by microrna-10b. Cancer Res. 2011, 71, 3563-3572.
74. Ma, L.; Teruya-Feldstein, J.; Weinberg, R.A. Tumour invasion and metastasis initiated by microrna-10b in breast cancer. Nature 2007, 449, 682-688.
75. Baffa, R.; Fassan, M.; Volinia, S.; O'Hara, B.; Liu, C.G.; Palazzo, J.P.; Gardiman, M.; Rugge, M.; Gomella, L.G.; Croce, C.M. et al. Microrna expression profiling of human metastatic cancers identifies cancer gene targets. J. Pathol. 2009, 219, 214-221.
76. Tan, H.X.; Wang, Q.; Chen, L.Z.; Huang, X.H.; Chen, J.S.; Fu, X.H.; Cao, L.Q.; Chen, X.L.; Li, W.; Zhang, L.J. Microrna-9 reduces cell invasion and e-cadherin secretion in sk-hep-1 cell. Med. Oncol. 2010, 27, 654-660.
77. Ciafre, S.A.; Galardi, S.; Mangiola, A.; Ferracin, M.; Liu, C.G.; Sabatino, G.; Negrini, M.; Maira, G.; Croce, C.M.; Farace, M.G. Extensive modulation of a set of micrornas in primary glioblastoma. Biochem. Biophys. Res. Commun. 2005, 334, 1351-1358.
78. Liu, Y.; Zhao, J.; Zhang, P.Y.; Zhang, Y.; Sun, S.Y.; Yu, S.Y.; Xi, Q.S. Microrna-10b targets e-cadherin and modulates breast cancer metastasis. Med. Sci. Monit. 2012, 18, BR299-BR308.
79. Hossain, A.; Kuo, M.T.; Saunders, G.F. Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of aib1 mrna. Mol. Cell. Biol. 2006, 26, 8191-8201.
80. Cheng, A.M.; Byrom, M.W.; Shelton, J.; Ford, L.P. Antisense inhibition of human mirnas and indications for an involvement of mirna in cell growth and apoptosis. Nucleic Acids Res. 2005, 33, 1290-1297.
81. Esau, C.C. Inhibition of microrna with antisense oligonucleotides. Methods 2008, 44, 55-60.
82. Lee, Y.S.; Kim, H.K.; Chung, S.; Kim, K.S.; Dutta, A. Depletion of human micro-rna mir-125b reveals that it is critical for the proliferation of differentiated cells but not for the down-regulation of putative targets during differentiation. J. Biol. Chem. 2005, 280, 16635-16641.
83. Kloosterman, W.P.; Lagendijk, A.K.; Ketting, R.F.; Moulton, J.D.; Plasterk, R.H. Targeted inhibition of mirna maturation with morpholinos reveals a role for mir-375 in pancreatic islet development. PLoS Biol. 2007, 5, e203.
84. Gantier, M.P.; McCoy, C.E.; Rusinova, I.; Saulep, D.; Wang, D.; Xu, D.; Irving, A.T.; Behlke, M.A.; Hertzog, P.J.; Mackay, F. et al. Analysis of microrna turnover in mammalian cells following dicer1 ablation. Nucleic Acids Res. 2011, 39, 5692-5703.
85. Lee, Y.; Hur, I.; Park, S.Y.; Kim, Y.K.; Suh, M.R.; Kim, V.N. The role of pact in the rna silencing pathway. EMBO J. 2006, 25, 522-532.
86. Zhang, B.; Farwell, M.A. Micrornas: A new emerging class of players for disease diagnostics and gene therapy. J. Cell. Mol. Med. 2008, 12, 3-21.
87. Hutvagner, G.; Simard, M.J.; Mello, C.C.; Zamore, P.D. Sequence-specific inhibition of small rna function. PLoS Biol. 2004, 2, E98.
88. Krutzfeldt, J.; Rajewsky, N.; Braich, R.; Rajeev, K.G.; Tuschl, T.; Manoharan, M.; Stoffel, M. Silencing of micrornas in vivo with "antagomirs". Nature 2005, 438, 685-689.
89. Esau, C.; Davis, S.; Murray, S.F.; Yu, X.X.; Pandey, S.K.; Pear, M.; Watts, L.; Booten, S.L.; Graham, M.; McKay, R. et al. Mir-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006, 3, 87-98.
90. Davis, S.; Lollo, B.; Freier, S.; Esau, C. Improved targeting of mirna with antisense oligonucleotides. Nucleic Acids Res. 2006, 34, 2294-2304.
91. Orom, U.A.; Kauppinen, S.; Lund, A.H. Lna-modified oligonucleotides mediate specific inhibition of microrna function. Gene 2006, 372, 137-141.
92. Nielsen, P.E.; Egholm, M.; Berg, R.H.; Buchardt, O. Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science 1991, 254, 1497-1500.
93. Fabbri, E.; Brognara, E.; Borgatti, M.; Lampronti, I.; Finotti, A.; Bianchi, N.; Sforza, S.; Tedeschi, T.; Manicardi, A.; Marchelli, R. et al. Mirna therapeutics: Delivery and biological activity of peptide nucleic acids targeting mirnas. Epigenomics 2011, 3, 733-745.
94. Torres, A.G.; Fabani, M.M.; Vigorito, E.; Williams, D.; Al-Obaidi, N.; Wojciechowski, F.; Hudson, R.H.; Seitz, O.; Gait, M.J. Chemical structure requirements and cellular targeting of microrna-122 by peptide nucleic acids anti-mirs. Nucleic Acids Res. 2011, 40, 2152-2167.
95. Shiraishi, T.; Nielsen, P.E. Cellular Bioavailability of Peptide Nucleic Acids (Pnas) Conjugated to Cell Penetrating Peptides. In Delivery Technologies for Biopharmaceuticals: Peptides, Proteins, Nucleic Acids and Vaccines; Jorgensen, L., Nielsen, H.M., Eds.; John Wiley and Sons Ltd: Hoboken, NJ, USA, 2009.
96. Babar, I.A.; Cheng, C.J.; Booth, C.J.; Liang, X.; Weidhaas, J.B.; Saltzman, W.M.; Slack, F.J. Nanoparticle-based therapy in an in vivo microrna-155 (mir-155)-dependent mouse model of lymphoma. Proc. Natl. Acad. Sci. USA 2012, 109, E1695-E1704.
97. Ebert, M.S.; Neilson, J.R.; Sharp, P.A. Microrna sponges: Competitive inhibitors of small rnas in mammalian cells. Nat. Methods 2007, 4, 721-726.
98. Kluiver, J.; Gibcus, J.H.; Hettinga, C.; Adema, A.; Richter, M.K.; Halsema, N.; Slezak-Prochazka, I.; Ding, Y.; Kroesen, B.J.; van den Berg, A. Rapid generation of microrna sponges for microrna inhibition. PLoS One 2012, 7, e29275.
99. Li, T.; Li, D.; Sha, J.; Sun, P.; Huang, Y. Microrna-21 directly targets marcks and promotes apoptosis resistance and invasion in prostate cancer cells. Biochem. Biophys. Res. Commun. 2009, 383, 280-285.
100. Si, M.L.; Zhu, S.; Wu, H.; Lu, Z.; Wu, F.; Mo, Y.Y. Mir-21-mediated tumor growth. Oncogene 2007, 26, 2799-2803.
101. Seike, M.; Goto, A.; Okano, T.; Bowman, E.D.; Schetter, A.J.; Horikawa, I.; Mathe, E.A.; Jen, J.; Yang, P.; Sugimura, H. et al. Mir-21 is an egfr-regulated anti-apoptotic factor in lung cancer in never-smokers. Proc. Natl. Acad. Sci. USA 2009, 106, 12085-12090.
102. Hatley, M.E.; Patrick, D.M.; Garcia, M.R.; Richardson, J.A.; Bassel-Duby, R.; van Rooij, E.; Olson, E.N. Modulation of k-ras-dependent lung tumorigenesis by microrna-21. Cancer Cell 2010, 18, 282-293.
103. Park, J.K.; Lee, E.J.; Esau, C.; Schmittgen, T.D. Antisense inhibition of microrna-21 or -221 arrests cell cycle, induces apoptosis, and sensitizes the effects of gemcitabine in pancreatic adenocarcinoma. Pancreas 2009, 38, e190-e199.
104. Basu, A.; Alder, H.; Khiyami, A.; Leahy, P.; Croce, C.M.; Haldar, S. Microrna-375 and microrna-221: Potential noncoding rnas associated with antiproliferative activity of benzyl isothiocyanate in pancreatic cancer. Genes Cancer 2011, 2, 108-119.
105. Park, J.K.; Kogure, T.; Nuovo, G.J.; Jiang, J.; He, L.; Kim, J.H.; Phelps, M.A.; Papenfuss, T.L.; Croce, C.M.; Patel, T. et al. Mir-221 silencing blocks hepatocellular carcinoma and promotes survival. Cancer Res. 2011, 71, 7608-7616.
106. Ma, L.; Reinhardt, F.; Pan, E.; Soutschek, J.; Bhat, B.; Marcusson, E.G.; Teruya-Feldstein, J.; Bell, G.W.; Weinberg, R.A. Therapeutic silencing of mir-10b inhibits metastasis in a mouse mammary tumor model. Nat. Biotechnol. 2010, 28, 341-347.
107. Henry, J.C.; Azevedo-Pouly, A.C.; Schmittgen, T.D. Microrna replacement therapy for cancer. Pharm. Res. 2011, 28, 3030-3042.
108. Behlke, M.A. Chemical modification of sirnas for in vivo use. Oligonucleotides 2008, 18, 305-319.
109. Choung, S.; Kim, Y.J.; Kim, S.; Park, H.O.; Choi, Y.C. Chemical modification of sirnas to improve serum stability without loss of efficacy. Biochem. Biophys. Res. Commun. 2006, 342, 919-927.
110. Prakash, T.P.; Allerson, C.R.; Dande, P.; Vickers, T.A.; Sioufi, N.; Jarres, R.; Baker, B.F.; Swayze, E.E.; Griffey, R.H.; Bhat, B. Positional effect of chemical modifications on short interference rna activity in mammalian cells. J. Med. Chem. 2005, 48, 4247-4253.
111. 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, 276-280.
112. Hamm, S.; Latz, E.; Hangel, D.; Muller, T.; Yu, P.; Golenbock, D.; Sparwasser, T.; Wagner, H.; Bauer, S. Alternating 2'-o-ribose methylation is a universal approach for generating non-stimulatory sirna by acting as tlr7 antagonist. Immunobiology 2010, 215, 559-569.
113. Chorn, G.; Klein-McDowell, M.; Zhao, L.; Saunders, M.A.; Flanagan, W.M.; Willingham, A.T.; Lim, L.P. Single-stranded microrna mimics. RNA 2012, 18, 1796-1804.
114. Esau, C.C.; Monia, B.P. Therapeutic potential for micrornas. Adv. Drug Deliv. Rev. 2007, 59, 101-114.
115. Liu, Y.P.; Berkhout, B. Mirna cassettes in viral vectors: Problems and solutions. Biochim. Biophys. Acta 2011, 1809, 732-745.
116. McManus, M.T.; Petersen, C.P.; Haines, B.B.; Chen, J.; Sharp, P.A. Gene silencing using micro-rna designed hairpins. RNA 2002, 8, 842-850.
117. Sibley, C.R.; Seow, Y.; Wood, M.J. Novel rna-based strategies for therapeutic gene silencing. Mol. Ther. 2010, 18, 466-476.
118. Grimm, D.; Kay, M.A. Rnai and gene therapy: A mutual attraction. Hematology Am. Soc. Hematol. Educ. Program. 2007, 473-481.
119. Boudreau, R.L.; Martins, I.; Davidson, B.L. Artificial micrornas as sirna shuttles: Improved safety as compared to shrnas in vitro and in vivo. Mol. Ther. 2009, 17, 169-175.
120. McBride, J.L.; Boudreau, R.L.; Harper, S.Q.; Staber, P.D.; Monteys, A.M.; Martins, I.; Gilmore, B.L.; Burstein, H.; Peluso, R.W.; Polisky, B. et al. Artificial mirnas mitigate shrna-mediated toxicity in the brain: Implications for the therapeutic development of rnai. Proc. Natl. Acad. Sci. USA 2008, 105, 5868-5873.
121. Jackson, A.L.; Burchard, J.; Schelter, J.; Chau, B.N.; Cleary, M.; Lim, L.; Linsley, P.S. Widespread sirna "Off-target" Transcript silencing mediated by seed region sequence complementarity. RNA 2006, 12, 1179-1187.
122. Liu, C.; Kelnar, K.; Liu, B.; Chen, X.; Calhoun-Davis, T.; Li, H.; Patrawala, L.; Yan, H.; Jeter, C.; Honorio, S. et al. The microrna mir-34a inhibits prostate cancer stem cells and metastasis by directly repressing cd44. Nat. Med. 2011, 17, 211-215.
123. Tazawa, H.; Tsuchiya, N.; Izumiya, M.; Nakagama, H. Tumor-suppressive mir-34a induces senescence-like growth arrest through modulation of the e2f pathway in human colon cancer cells. Proc. Natl. Acad. Sci. USA 2007, 104, 15472-15477.
124. Li, L.; Xie, X.; Luo, J.; Liu, M.; Xi, S.; Guo, J.; Kong, Y.; Wu, M.; Gao, J.; Xie, Z. et al. Targeted expression of mir-34a using the t-visa system suppresses breast cancer cell growth and invasion. Mol. Ther. 2012, 20, 2326-2334.
125. Takamizawa, J.; Konishi, H.; Yanagisawa, K.; Tomida, S.; Osada, H.; Endoh, H.; Harano, T.; Yatabe, Y.; Nagino, M.; Nimura, Y. et al. Reduced expression of the let-7 micrornas in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004, 64, 3753-3756.
126. Johnson, C.D.; Esquela-Kerscher, A.; Stefani, G.; Byrom, M.; Kelnar, K.; Ovcharenko, D.; Wilson, M.; Wang, X.; Shelton, J.; Shingara, J. et al. The let-7 microrna represses cell proliferation pathways in human cells. Cancer Res. 2007, 67, 7713-7722.
127. Marquez, R.T.; McCaffrey, A.P. Advances in micrornas: Implications for gene therapists. Hum. Gene Ther. 2008, 19, 27-38.
128. Kefas, B.; Godlewski, J.; Comeau, L.; Li, Y.; Abounader, R.; Hawkinson, M.; Lee, J.; Fine, H.; Chiocca, E.A.; Lawler, S. et al. Microrna-7 inhibits the epidermal growth factor receptor and the akt pathway and is down-regulated in glioblastoma. Cancer Res. 2008, 68, 3566-3572.
129. Zhang, Y.; Chao, T.; Li, R.; Liu, W.; Chen, Y.; Yan, X.; Gong, Y.; Yin, B.; Qiang, B.; Zhao, J. et al. Microrna-128 inhibits glioma cells proliferation by targeting transcription factor e2f3a. J. Mol. Med. 2009, 87, 43-51.
130. Jopling, C.L.; Yi, M.; Lancaster, A.M.; Lemon, S.M.; Sarnow, P. Modulation of hepatitis c virus rna abundance by a liver-specific microrna. Science 2005, 309, 1577-1581.
131. Lanford, R.E.; Hildebrandt-Eriksen, E.S.; Petri, A.; Persson, R.; Lindow, M.; Munk, M.E.; Kauppinen, S.; Orum, H. Therapeutic silencing of microrna-122 in primates with chronic hepatitis c virus infection. Science 2010, 327, 198-201.
132. Lindow, M.; Kauppinen, S. Discovering the first microrna-targeted drug. J. Cell Biol. 2012, 199, 407-412.
133. Bader, A.G. Mir-34-A microrna replacement therapy is headed to the clinic. Front. Genet. 2012, 3, 120.
134. Banks, W.A.; Farr, S.A.; Butt, W.; Kumar, V.B.; Franko, M.W.; Morley, J.E. Delivery across the blood-brain barrier of antisense directed against amyloid beta: Reversal of learning and memory deficits in mice overexpressing amyloid precursor protein. J. Pharmacol. Exp. Ther. 2001, 297, 1113-1121.
135. Catuogno, S.; Esposito, C.L.; Quintavalle, C.; Condorelli, G.; de Franciscis, V.; Cerchia, L. Nucleic acids in human glioma treatment: Innovative approaches and recent results. J. Signal. Transduct. 2012, 2012, 735135.
136. Du, L.; Kayali, R.; Bertoni, C.; Fike, F.; Hu, H.; Iversen, P.L.; Gatti, R.A. Arginine-rich cell-penetrating peptide dramatically enhances amo-mediated atm aberrant splicing correction and enables delivery to brain and cerebellum. Hum. Mol. Genet. 2011, 20, 3151-3160.
137. Xia, H.; Mao, Q.; Paulson, H.L.; Davidson, B.L. Sirna-mediated gene silencing in vitro and in vivo. Nat. Biotechnol. 2002, 20, 1006-1010.
138. Lu, P.Y.; Xie, F.; Woodle, M.C. In vivo application of rna interference: From functional genomics to therapeutics. Adv. Genet. 2005, 54, 117-142.
139. Tong, A.W. Small rnas and non-small cell lung cancer. Curr. Mol. Med. 2006, 6, 339-349.
140. Kota, J.; Chivukula, R.R.; O'Donnell, K.A.; Wentzel, E.A.; Montgomery, C.L.; Hwang, H.W.; Chang, T.C.; Vivekanandan, P.; Torbenson, M.; Clark, K.R. et al. Therapeutic microrna delivery suppresses tumorigenesis in a murine liver cancer model. Cell 2009, 137, 1005-1017.
141. Trang, P.; Medina, P.P.; Wiggins, J.F.; Ruffino, L.; Kelnar, K.; Omotola, M.; Homer, R.; Brown, D.; Bader, A.G.; Weidhaas, J.B. et al. Regression of murine lung tumors by the let-7 microrna. Oncogene 2010, 29, 1580-1587.
142. Bonci, D.; Coppola, V.; Musumeci, M.; Addario, A.; Giuffrida, R.; Memeo, L.; D'Urso, L.; Pagliuca, A.; Biffoni, M.; Labbaye, C. et al. The mir-15a-mir-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat. Med. 2008, 14, 1271-1277.
143. Sicard, F.; Gayral, M.; Lulka, H.; Buscail, L.; Cordelier, P. Targeting mir-21 for the therapy of pancreatic cancer. Mol. Ther. 2013, 21, 986-994.
144. Lee, S.J.; Kim, S.J.; Seo, H.H.; Shin, S.P.; Kim, D.; Park, C.S.; Kim, K.T.; Kim, Y.H.; Jeong, J.S.; Kim, I.H. Over-expression of mir-145 enhances the effectiveness of hsvtk gene therapy for malignant glioma. Cancer Lett. 2012, 320, 72-80.
145. Wang, X.; Han, L.; Zhang, A.; Wang, G.; Jia, Z.; Yang, Y.; Yue, X.; Pu, P.; Shen, C.; Kang, C. Adenovirus-mediated shrnas for co-repression of mir-221 and mir-222 expression and function in glioblastoma cells. Oncol. Rep. 2011, 25, 97-105.
146. Pramanik, D.; Campbell, N.R.; Karikari, C.; Chivukula, R.; Kent, O.A.; Mendell, J.T.; Maitra, A. Restitution of tumor suppressor micrornas using a systemic nanovector inhibits pancreatic cancer growth in mice. Mol. Cancer Ther. 2011, 10, 1470-1480.
147. Trang, P.; Wiggins, J.F.; Daige, C.L.; Cho, C.; Omotola, M.; Brown, D.; Weidhaas, J.B.; Bader, A.G.; Slack, F.J. Systemic delivery of tumor suppressor microrna mimics using a neutral lipid emulsion inhibits lung tumors in mice. Mol. Ther. 2011, 19, 1116-1122.
148. Costa, P.M.; Cardoso, A.L.; Mendonca, L.S.; Serani, A.; Custodia, C.; Conceicao, M.; Simoes, S.; Moreira, J.N.; Pereira de Almeida, L.; Pedroso de Lima, M.C. Tumor-targeted chlorotoxin-coupled nanoparticles for nucleic acid delivery to glioblastoma cells: A promising system for glioblastoma treatment. Mol. Ther. Nucleic Acids 2013, 2, e100.
149. Yang, Y.P.; Chien, Y.; Chiou, G.Y.; Cherng, J.Y.; Wang, M.L.; Lo, W.L.; Chang, Y.L.; Huang, P.I.; Chen, Y.W.; Shih, Y.H. et al. Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microrna145 with cationic polyurethane-short branch pei. Biomaterials 2012, 33, 1462-1476.
150. Ren, Y.; Kang, C.S.; Yuan, X.B.; Zhou, X.; Xu, P.; Han, L.; Wang, G.X.; Jia, Z.; Zhong, Y.; Yu, S. et al. Co-delivery of as-mir-21 and 5-fu by poly(amidoamine) dendrimer attenuates human glioma cell growth in vitro. J. Biomater. Sci. Polym. Ed. 2010, 21, 303-314.
151. A Multicenter Phase I Study of MRX34, MicroRNA miR-RX34 Liposome Injectable Suspension. Available online: http://clinicaltrials.gov/ct2/show/NCT01829971/ (accessed on 23 September 2013).
152. Guan, J.; Fujimoto, K.L.; Sacks, M.S.; Wagner, W.R. Preparation and characterization of highly porous, biodegradable polyurethane scaffolds for soft tissue applications. Biomaterials 2005, 26, 3961-3971.
153. Liu, X.Y.; Ho, W.Y.; Hung, W.J.; Shau, M.D. The characteristics and transfection efficiency of cationic poly (ester-co-urethane)-Short chain pei conjugates self-assembled with DNA. Biomaterials 2009, 30, 6665-6673.
154. Bala, I.; Hariharan, S.; Kumar, M.N. Plga nanoparticles in drug delivery: The state of the art. Crit. Rev. Ther. Drug Carrier Syst. 2004, 21, 387-422.
155. Pettit, M.W.; Griffiths, P.; Ferruti, P.; Richardson, S.C. Poly(amidoamine) polymers: Soluble linear amphiphilic drug-delivery systems for genes, proteins and oligonucleotides. Ther. Deliv. 2011, 2, 907-917.
156. D'Emanuele, A.; Attwood, D. Dendrimer-drug interactions. Adv. Drug Deliv. Rev. 2005, 57