microRNA Therapeutics in Cancer — An Emerging Concept

EBioMedicine

Volumn 12, Issue , 2016, Pages 34-42

  Shah, Maitri Y ^a   Ferrajoli, Alessandra ^a   Sood, Anil K ^a   Lopez Berestein, Gabriel ^a   Calin, George A ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

Cancer; Clinical trials; microRNA; Non coding RNA; Therapeutics

Indexed keywords

ANTAGOMIR; ANTAGOMIR 122; ANTI MICRORNA ANTISENSE OLIGODEOXYRIBONUCLEOTIDE; ANTISENSE OLIGONUCLEOTIDE; DOUBLE STRANDED RNA; MICRORNA; MICRORNA 155; MICRORNA 15A; MICRORNA 16 MIMIC; MICRORNA 29B MIMIC; MIRAVIRSEN; MRG 106; MRG 201; MRX 34; PEPTIDOMIMETIC AGENT; PROTEIN INHIBITOR; SMALL MOLECULE INHIBITOR OF MIRNA; UNCLASSIFIED DRUG;

CANCER SURVIVAL; CANCER THERAPY; CARCINOGENESIS; CELL MIGRATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; EXOSOME; HEPATITIS C; HUMAN; MEMBRANE MICROPARTICLE; NON SMALL CELL LUNG CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PLEURA MESOTHELIOMA; PRIORITY JOURNAL; REVIEW; SCLERODERMA; SOLID TUMOR; TUMOR SUPPRESSOR GENE; ADVERSE EFFECTS; ANIMAL; CLINICAL TRIAL (TOPIC); GENE EXPRESSION REGULATION; GENE SILENCING; GENE THERAPY; GENETICS; IMMUNOLOGY; IMMUNOMODULATION; NEOPLASMS; PATHOLOGY; PRECLINICAL STUDY; PROCEDURES; RNA INTERFERENCE; TREATMENT OUTCOME; TUMOR MICROENVIRONMENT;

ANIMALS; CLINICAL TRIALS AS TOPIC; DRUG EVALUATION, PRECLINICAL; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE SILENCING; GENETIC THERAPY; HUMANS; IMMUNOMODULATION; MICRORNAS; NEOPLASMS; RNA INTERFERENCE; TREATMENT OUTCOME; TUMOR MICROENVIRONMENT;

EID: 84992672488     PISSN: None     EISSN: 23523964     Source Type: Journal    
DOI: 10.1016/j.ebiom.2016.09.017     Document Type: Review

References (93)

1. Alexander, M., Hu, R., Runtsch, M.C., Kagele, D.A., Mosbruger, T.L., Tolmachova, T., Seabra, M.C., Round, J.L., Ward, D.M., O'connell, R.M., Exosome-delivered microRNAs modulate the inflammatory response to endotoxin. Nat. Commun., 6, 2015, 7321.
2. Aprelikova, O., Yu, X., Palla, J., Wei, B.R., John, S., Yi, M., Stephens, R., Simpson, R.M., Risinger, J.I., Jazaeri, A., Niederhuber, J., The role of miR-31 and its target gene SATB2 in cancer-associated fibroblasts. Cell Cycle 9 (2010), 4387–4398.
3. Bandres, E., Agirre, X., Bitarte, N., Ramirez, N., Zarate, R., Roman-Gomez, J., Prosper, F., Garcia-Foncillas, J., Epigenetic regulation of microRNA expression in colorectal cancer. Int. J. Cancer 125 (2009), 2737–2743.
4. Bartel, D.P., MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116 (2004), 281–297.
5. Berindan-Neagoe, I., Monroig Pdel, C., Pasculli, B., Calin, G.A., MicroRNAome genome: a treasure for cancer diagnosis and therapy. CA Cancer J. Clin. 64 (2014), 311–336.
6. Bonci, D., Coppola, V., Musumeci, M., Addario, A., Giuffrida, R., Memeo, L., D'urso, L., Pagliuca, A., Biffoni, M., Labbaye, C., Bartucci, M., Muto, G., Peschle, C., de Maria, R., The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat. Med. 14 (2008), 1271–1277.
7. Calin, G.A., Croce, C.M., Genomics of chronic lymphocytic leukemia microRNAs as new players with clinical significance. Semin. Oncol. 33 (2006), 167–173.
8. Calin, G.A., Croce, C.M., MicroRNA signatures in human cancers. Nat. Rev. Cancer 6 (2006), 857–866.
9. Calin, G.A., Croce, C.M., Chronic lymphocytic leukemia: interplay between noncoding RNAs and protein-coding genes. Blood 114 (2009), 4761–4770.
10. Calin, G.A., Sevignani, C., Dumitru, C.D., Hyslop, T., Noch, E., Yendamuri, S., Shimizu, M., Rattan, S., Bullrich, F., Negrini, M., Croce, C.M., Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc. Natl. Acad. Sci. U. S. A. 101 (2004), 2999–3004.
11. Carstens, J.L., Lovisa, S., Kalluri, R., Microenvironment-dependent cues trigger miRNA-regulated feedback loop to facilitate the EMT/MET switch. J. Clin. Invest. 124 (2014), 1458–1460.
12. Chaluvally-Raghavan, P., Jeong, K.J., Pradeep, S., Silva, A.M., Yu, S., Liu, W., Moss, T., Rodriguez-Aguayo, C., Zhang, D., Ram, P., Liu, J., Lu, Y., Lopez-Berestein, G., Calin, G.A., Sood, A.K., Mills, G.B., Direct upregulation of STAT3 by MicroRNA-551b-3p deregulates growth and metastasis of ovarian cancer. Cell Rep. 15 (2016), 1493–1504.
13. Chan, S.Y., Zhang, Y.Y., Hemann, C., Mahoney, C.E., Zweier, J.L., Loscalzo, J., MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2. Cell Metab. 10 (2009), 273–284.
14. Chang, T.C., Wentzel, E.A., Kent, O.A., Ramachandran, K., Mullendore, M., Lee, K.H., Feldmann, G., Yamakuchi, M., Ferlito, M., Lowenstein, C.J., Arking, D.E., Beer, M.A., Maitra, A., Mendell, J.T., Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol. Cell 26 (2007), 745–752.
15. Chang, T.C., Yu, D., Lee, Y.S., Wentzel, E.A., Arking, D.E., West, K.M., Dang, C.V., Thomas-Tikhonenko, A., Mendell, J.T., Widespread microRNA repression by Myc contributes to tumorigenesis. Nat. Genet. 40 (2008), 43–50.
16. Chou, J., Shahi, P., Werb, Z., microRNA-mediated regulation of the tumor microenvironment. Cell Cycle 12 (2013), 3262–3271.
17. Chung, K.H., Hart, C.C., Al-Bassam, S., Avery, A., Taylor, J., Patel, P.D., Vojtek, A.B., Turner, D.L., Polycistronic RNA polymerase II expression vectors for RNA interference based on BIC/miR-155. Nucleic Acids Res., 34, 2006, e53.
18. Cortez, M.A., Ivan, C., Valdecanas, D., Wang, X., Peltier, H.J., Ye, Y., Araujo, L., Carbone, D.P., Shilo, K., Giri, D.K., Kelnar, K., Martin, D., Komaki, R., Gomez, D.R., Krishnan, S., Calin, G.A., Bader, A.G., Welsh, J.W., PDL1 regulation by p53 via miR-34. J. Natl. Cancer Inst., 108, 2016.
19. Costinean, S., Zanesi, N., Pekarsky, Y., Tili, E., Volinia, S., Heerema, N., Croce, C.M., Pre-B cell proliferation and lymphoblastic leukemia/high-grade lymphoma in E(mu)-miR155 transgenic mice, Proceedings of the National Academy of Sciences of the United States of America, 103, 2006, 7024–7029.
20. Dalmay, T., Edwards, D.R., MicroRNAs and the hallmarks of cancer. Oncogene 25 (2006), 6170–6175.
21. Das, S., Ferlito, M., Kent, O.A., Fox-Talbot, K., Wang, R., Liu, D., Raghavachari, N., Yang, Y., Wheelan, S.J., Murphy, E., Steenbergen, C., Nuclear miRNA regulates the mitochondrial genome in the heart. Circ. Res. 110 (2012), 1596–1603.
22. Ebert, M.S., Neilson, J.R., Sharp, P.A., MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat. Methods 4 (2007), 721–726.
23. Eiring, A.M., Harb, J.G., Neviani, P., Garton, C., Oaks, J.J., Spizzo, R., Liu, S., Schwind, S., Santhanam, R., Hickey, C.J., Becker, H., Chandler, J.C., Andino, R., Cortes, J., Hokland, P., Huettner, C.S., Bhatia, R., Roy, D.C., Liebhaber, S.A., Caligiuri, M.A., Marcucci, G., Garzon, R., Croce, C.M., Calin, G.A., Perrotti, D., miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell 140 (2010), 652–665.
24. Elmen, J., Lindow, M., Schutz, S., Lawrence, M., Petri, A., Obad, S., Lindholm, M., Hedtjarn, M., Hansen, H.F., Berger, U., Gullans, S., Kearney, P., Sarnow, P., Straarup, E.M., Kauppinen, S., LNA-mediated microRNA silencing in non-human primates. Nature 452 (2008), 896–899.
25. Esau, C., Davis, S., Murray, S.F., Yu, X.X., Pandey, S.K., Pear, M., Watts, L., Booten, S.L., Graham, M., Mckay, R., Subramaniam, A., Propp, S., Lollo, B.A., Freier, S., Bennett, C.F., Bhanot, S., Monia, B.P., miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 3 (2006), 87–98.
26. Esposito, C.L., Cerchia, L., Catuogno, S., De Vita, G., Dassie, J.P., Santamaria, G., Swiderski, P., Condorelli, G., Giangrande, P.H., De Franciscis, V., Multifunctional aptamer-miRNA conjugates for targeted cancer therapy. Mol. Ther. 22 (2014), 1151–1163.
27. 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 7 (2008), 759–764.
28. Fabbri, M., Paone, A., Calore, F., Galli, R., Gaudio, E., Santhanam, R., Lovat, F., Fadda, P., Mao, C., Nuovo, G.J., Zanesi, N., Crawford, M., Ozer, G.H., Wernicke, D., Alder, H., Caligiuri, M.A., Nana-Sinkam, P., Perrotti, D., Croce, C.M., MicroRNAs bind to toll-like receptors to induce prometastatic inflammatory response. Proc. Natl. Acad. Sci. U. S. A. 109 (2012), E2110–E2116.
29. Filipowicz, W., Bhattacharyya, S.N., Sonenberg, N., Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?. Nat. Rev. Genet. 9 (2008), 102–114.
30. Gallo Cantafio, M.E., Nielsen, B.S., Mignogna, C., Arbitrio, M., Botta, C., Frandsen, N.M., Rolfo, C., Tagliaferri, P., Tassone, P., Di Martino, M.T., Pharmacokinetics and pharmacodynamics of a 13-mer LNA-inhibitor-miR-221 in mice and non-human primates. Mol. Ther.–Nucleic Acids, 5, 2016.
31. Garzon, R., Marcucci, G., Croce, C.M., Targeting microRNAs in cancer: rationale, strategies and challenges. Nat. Rev. Drug Discov. 9 (2010), 775–789.
32. Gaur, S., Wen, Y., Song, J.H., Parikh, N.U., Mangala, L.S., Blessing, A.M., Ivan, C., Wu, S.Y., Varkaris, A., Shi, Y., Lopez-Berestein, G., Frigo, D.E., Sood, A.K., Gallick, G.E., Chitosan nanoparticle-mediated delivery of miRNA-34a decreases prostate tumor growth in the bone and its expression induces non-canonical autophagy. Oncotarget 6 (2015), 29161–29177.
33. Griveau, A., Bejaud, J., Anthiya, S., Avril, S., Autret, D., Garcion, E., Silencing of miR-21 by locked nucleic acid-lipid nanocapsule complexes sensitize human glioblastoma cells to radiation-induced cell death. Int. J. Pharm. 454 (2013), 765–774.
34. Gumireddy, K., Young, D.D., Xiong, X., Hogenesch, J.B., Huang, Q., Deiters, A., Small-molecule inhibitors of microrna miR-21 function. Angew. Chem. 47 (2008), 7482–7484.
35. Han, H.D., Mangala, L.S., Lee, J.W., Shahzad, M.M., Kim, H.S., Shen, D., Nam, E.J., Mora, E.M., Stone, R.L., Lu, C., Lee, S.J., Roh, J.W., Nick, A.M., Lopez-Berestein, G., Sood, A.K., Targeted gene silencing using RGD-labeled chitosan nanoparticles. Clin. Cancer Res. 16 (2010), 3910–3922.
36. Hanahan, D., Weinberg, R.A., The hallmarks of cancer. Cell 100 (2000), 57–70.
37. Hanahan, D., Weinberg, R.A., Hallmarks of cancer: the next generation. Cell 144 (2011), 646–674.
38. Hildebrandt, M.A., Gu, J., Lin, J., Ye, Y., Tan, W., Tamboli, P., Wood, C.G., Wu, X., Hsa-miR-9 methylation status is associated with cancer development and metastatic recurrence in patients with clear cell renal cell carcinoma. Oncogene 29 (2010), 5724–5728.
39. Hutvagner, G., Simard, M.J., Mello, C.C., Zamore, P.D., Sequence-specific inhibition of small RNA function. PLoS Biol., 2, 2004, E98.
40. Hwang, H.W., Wentzel, E.A., Mendell, J.T., A hexanucleotide element directs microRNA nuclear import. Science 315 (2007), 97–100.
41. Janssen, H.L., Reesink, H.W., Lawitz, E.J., Zeuzem, S., Rodriguez-Torres, M., Patel, K., Van Der Meer, A.J., Patick, A.K., Chen, A., Zhou, Y., Persson, R., King, B.D., Kauppinen, S., Levin, A.A., Hodges, M.R., Treatment of HCV infection by targeting microRNA. N. Engl. J. Med. 368 (2013), 1685–1694.
42. Ji, M., Rao, E., Ramachandrareddy, H., Shen, Y., Jiang, C., Chen, J., Hu, Y., Rizzino, A., Chan, W.C., Fu, K., Mckeithan, T.W., The miR-17-92 microRNA cluster is regulated by multiple mechanisms in B-cell malignancies. Am. J. Pathol. 179 (2011), 1645–1656.
43. Kim, V.N., MicroRNA biogenesis: coordinated cropping and dicing. Nat. Rev. Mol. Cell Biol. 6 (2005), 376–385.
44. Kim, D.H., Saetrom, P., Snove, O. Jr., Rossi, J.J., MicroRNA-directed transcriptional gene silencing in mammalian cells. Proc. Natl. Acad. Sci. U. S. A. 105 (2008), 16230–16235.
45. Klein, U., Lia, M., Crespo, M., Siegel, R., Shen, Q., Mo, T., Ambesi-Impiombato, A., Califano, A., Migliazza, A., Bhagat, G., Dalla-Favera, R., The DLEU2/miR-15a/16-1 cluster controls B cell proliferation and its deletion leads to chronic lymphocytic leukemia. Cancer Cell 17 (2010), 28–40.
46. Korpal, M., Ell, B.J., Buffa, F.M., Ibrahim, T., Blanco, M.A., Celia-Terrassa, T., Mercatali, L., Khan, Z., Goodarzi, H., Hua, Y., Wei, Y., Hu, G., Garcia, B.A., Ragoussis, J., Amadori, D., Harris, A.L., Kang, Y., Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat. Med. 17 (2011), 1101–1108.
47. Kosaka, N., Iguchi, H., Yoshioka, Y., Takeshita, F., Matsuki, Y., Ochiya, T., Secretory mechanisms and intercellular transfer of microRNAs in living cells. J. Biol. Chem. 285 (2010), 17442–17452.
48. Krutzfeldt, J., Rajewsky, N., Braich, R., Rajeev, K.G., Tuschl, T., Manoharan, M., Stoffel, M., Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438 (2005), 685–689.
49. Lee, R.C., Feinbaum, R.L., Ambros, V., The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75 (1993), 843–854.
50. Lehmann, S.M., Kruger, C., Park, B., Derkow, K., Rosenberger, K., Baumgart, J., Trimbuch, T., Eom, G., Hinz, M., Kaul, D., Habbel, P., Kalin, R., Franzoni, E., Rybak, A., Nguyen, D., Veh, R., Ninnemann, O., Peters, O., Nitsch, R., Heppner, F.L., Golenbock, D., Schott, E., Ploegh, H.L., Wulczyn, F.G., Lehnardt, S., An unconventional role for miRNA: let-7 activates toll-like receptor 7 and causes neurodegeneration. Nat. Neurosci. 15 (2012), 827–835.
51. Li, Y.P., Van Pham, L., Uzcategui, N., Bukh, J., Functional analysis of microRNA-122 binding sequences of hepatitis C virus and identification of variants with high resistance against a specific antagomir. J. Gen. Virol. 97 (2016), 1381–1394.
52. Lieberman, J., Sarnow, P., Micromanaging hepatitis C virus. N. Engl. J. Med. 368 (2013), 1741–1743.
53. Liu, J., Wu, C.P., Lu, B.F., Jiang, J.T., Mechanism of T cell regulation by microRNAs. Cancer Biol. Med. 10 (2013), 131–137.
54. Lodygin, D., Tarasov, V., Epanchintsev, A., Berking, C., Knyazeva, T., Korner, H., Knyazev, P., Diebold, J., Hermeking, H., Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell Cycle 7 (2008), 2591–2600.
55. Lujambio, A., Ropero, S., Ballestar, E., Fraga, M.F., Cerrato, C., Setien, F., Casado, S., Suarez-Gauthier, A., Sanchez-Cespedes, M., Git, A., Spiteri, I., Das, P.P., Caldas, C., Miska, E., Esteller, M., Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res. 67 (2007), 1424–1429.
56. Lujambio, A., Calin, G.A., Villanueva, A., Ropero, S., Sanchez-Cespedes, M., Blanco, D., Montuenga, L.M., Rossi, S., Nicoloso, M.S., Faller, W.J., Gallagher, W.M., Eccles, S.A., Croce, C.M., Esteller, M., A microRNA DNA methylation signature for human cancer metastasis. Proc. Natl. Acad. Sci. U. S. A. 105 (2008), 13556–13561.
57. Luo, S.S., Ishibashi, O., Ishikawa, G., Ishikawa, T., Katayama, A., Mishima, T., Takizawa, T., Shigihara, T., Goto, T., Izumi, A., Ohkuchi, A., Matsubara, S., Takeshita, T., Takizawa, T., Human villous trophoblasts express and secrete placenta-specific microRNAs into maternal circulation via exosomes. Biol. Reprod. 81 (2009), 717–729.
58. Ma, L., Young, J., Prabhala, H., Pan, E., Mestdagh, P., Muth, D., Teruya-Feldstein, J., Reinhardt, F., Onder, T.T., Valastyan, S., Westermann, F., Speleman, F., Vandesompele, J., Weinberg, R.A., miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat. Cell Biol. 12 (2010), 247–256.
59. Medina, P.P., Nolde, M., Slack, F.J., OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature 467 (2010), 86–90.
60. Melo, S., Villanueva, A., Moutinho, C., Davalos, V., Spizzo, R., Ivan, C., Rossi, S., Setien, F., Casanovas, O., Simo-Riudalbas, L., Carmona, J., Carrere, J., Vidal, A., Aytes, A., Puertas, S., Ropero, S., Kalluri, R., Croce, C.M., Calin, G.A., Esteller, M., Small molecule enoxacin is a cancer-specific growth inhibitor that acts by enhancing TAR RNA-binding protein 2-mediated microRNA processing. Proc. Natl. Acad. Sci. U. S. A. 108 (2011), 4394–4399.
61. 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 133 (2007), 647–658.
62. Mitra, A.K., Zillhardt, M., Hua, Y., Tiwari, P., Murmann, A.E., Peter, M.E., Lengyel, E., MicroRNAs reprogram normal fibroblasts into cancer-associated fibroblasts in ovarian cancer. Cancer Discov. 2 (2012), 1100–1108.
63. Mittelbrunn, M., Gutierrez-Vazquez, C., Villarroya-Beltri, C., Gonzalez, S., Sanchez-Cabo, F., Gonzalez, M.A., Bernad, A., Sanchez-Madrid, F., Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat. Commun., 2, 2011, 282.
64. Molitoris, J.K., Mccoll, K.S., Distelhorst, C.W., Glucocorticoid-mediated repression of the oncogenic microRNA cluster miR-17 ~ 92 contributes to the induction of Bim and initiation of apoptosis. Mol. Endocrinol. 25 (2011), 409–420.
65. Monroig Pdel, C., Chen, L., Zhang, S., Calin, G.A., Small molecule compounds targeting miRNAs for cancer therapy. Adv. Drug Deliv. Rev. 81 (2015), 104–116.
66. Negrini, M., Nicoloso, M.S., Calin, G.A., MicroRNAs and cancer—new paradigms in molecular oncology. Curr. Opin. Cell Biol. 21 (2009), 470–479.
67. Nicoloso, M.S., Spizzo, R., Shimizu, M., Rossi, S., Calin, G.A., MicroRNAs—the micro steering wheel of tumour metastases. Nat. Rev. Cancer 9 (2009), 293–302.
68. Nishimura, M., Jung, E.J., Shah, M.Y., Lu, C., Spizzo, R., Shimizu, M., Han, H.D., Ivan, C., Rossi, S., Zhang, X., Nicoloso, M.S., Wu, S.Y., Almeida, M.I., Bottsford-Miller, J., Pecot, C.V., Zand, B., Matsuo, K., Shahzad, M.M., Jennings, N.B., Rodriguez-Aguayo, C., Lopez-Berestein, G., Sood, A.K., Calin, G.A., Therapeutic synergy between microRNA and siRNA in ovarian cancer treatment. Cancer Discov 3 (2013), 1302–1315.
69. Orom, U.A., Nielsen, F.C., Lund, A.H., MicroRNA-10a binds the 5′UTR of ribosomal protein mRNAs and enhances their translation. Mol. Cell 30 (2008), 460–471.
70. Ottosen, S., Parsley, T.B., Yang, L., Zeh, K., van Doorn, L.J., van der Veer, E., Raney, A.K., Hodges, M.R., Patick, A.K., In vitro antiviral activity and preclinical and clinical resistance profile of miravirsen, a novel anti-hepatitis C virus therapeutic targeting the human factor miR-122. Antimicrob. Agents Chemother. 59 (2015), 599–608.
71. Pecot, C.V., Rupaimoole, R., Yang, D., Akbani, R., Ivan, C., Lu, C., Wu, S., Han, H.D., Shah, M.Y., Rodriguez-Aguayo, C., Bottsford-Miller, J., Liu, Y., Kim, S.B., Unruh, A., Gonzalez-Villasana, V., Huang, L., Zand, B., Moreno-Smith, M., Mangala, L.S., Taylor, M., Dalton, H.J., Sehgal, V., Wen, Y., Kang, Y., Baggerly, K.A., Lee, J.S., Ram, P.T., Ravoori, M.K., Kundra, V., Zhang, X., Ali-Fehmi, R., Gonzalez-Angulo, A.M., Massion, P.P., Calin, G.A., Lopez-Berestein, G., Zhang, W., Sood, A.K., Tumour angiogenesis regulation by the miR-200 family. Nat. Commun., 4, 2013, 2427.
72. Rakheja, D., Chen, K.S., Liu, Y., Shukla, A.A., Schmid, V., Chang, T.C., Khokhar, S., Wickiser, J.E., Karandikar, N.J., Malter, J.S., Mendell, J.T., Amatruda, J.F., Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis through distinct mechanisms in Wilms tumours. Nat. Commun., 2, 2014, 4802.
73. Schetter, A.J., Heegaard, N.H., Harris, C.C., Inflammation and cancer: interweaving microRNA, free radical, cytokine and p53 pathways. Carcinogenesis 31 (2010), 37–49.
74. Shah, M.Y., Calin, G.A., The mix of two worlds: non-coding RNAs and hormones. Nucleic Acid Ther. 23 (2013), 2–8.
75. Stern-Ginossar, N., Gur, C., Biton, M., Horwitz, E., Elboim, M., Stanietsky, N., Mandelboim, M., Mandelboim, O., Human microRNAs regulate stress-induced immune responses mediated by the receptor NKG2D. Nat. Immunol. 9 (2008), 1065–1073.
76. Tay, Y., Zhang, J., Thomson, A.M., Lim, B., Rigoutsos, I., MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455 (2008), 1124–1128.
77. Tili, E., Michaille, J.J., Croce, C.M., MicroRNAs play a central role in molecular dysfunctions linking inflammation with cancer. Immunol. Rev. 253 (2013), 167–184.
78. Tominaga, N., Kosaka, N., Ono, M., Katsuda, T., Yoshioka, Y., Tamura, K., Lotvall, J., Nakagama, H., Ochiya, T., Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood-brain barrier. Nat. Commun., 6, 2015, 6716.
79. Trang, P., Medina, P.P., Wiggins, J.F., Ruffino, L., Kelnar, K., Omotola, M., Homer, R., Brown, D., Bader, A.G., Weidhaas, J.B., Slack, F.J., Regression of murine lung tumors by the let-7 microRNA. Oncogene 29 (2010), 1580–1587.
80. Tsai, K.W., Liao, Y.L., Wu, C.W., Hu, L.Y., Li, S.C., Chan, W.C., Ho, M.R., Lai, C.H., Kao, H.W., Fang, W.L., Huang, K.H., Lin, W.C., Aberrant hypermethylation of miR-9 genes in gastric cancer. Epigenetics 6 (2011), 1189–1197.
81. Ueda, R., Kohanbash, G., Sasaki, K., Fujita, M., Zhu, X., Kastenhuber, E.R., Mcdonald, H.A., Potter, D.M., Hamilton, R.L., Lotze, M.T., Khan, S.A., Sobol, R.W., Okada, H., Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1. Proc. Natl. Acad. Sci. U. S. A. 106 (2009), 10746–10751.
82. Valencia-Sanchez, M.A., Liu, J., Hannon, G.J., Parker, R., Control of translation and mRNA degradation by miRNAs and siRNAs. Genes Dev. 20 (2006), 515–524.
83. Valeri, N., Gasparini, P., Fabbri, M., Braconi, C., Veronese, A., Lovat, F., Adair, B., Vannini, I., Fanini, F., Bottoni, A., Costinean, S., Sandhu, S.K., Nuovo, G.J., Alder, H., Gafa, R., Calore, F., Ferracin, M., Lanza, G., Volinia, S., Negrini, M., Mcilhatton, M.A., Amadori, D., Fishel, R., Croce, C.M., Modulation of mismatch repair and genomic stability by miR-155, Proceedings of the National Academy of Sciences of the United States of America, 107, 2010, 6982–6987.
84. Van Zandwijk, N., Pavlakis, N., Kao, S., Clarke, S., Lee, A., Brahmbhatt, H., Macdiarmid, J., Pattison, S., Leslie, F., Huynh, Y., Linton, A., Reid, G., P1.02, MesomiR 1: a phase I study of TargomiRs in patients with refractory malignant pleural mesothelioma (MPM) and lung cancer (NSCLC). Ann. Oncol., 26(suppl 2), 2015, ii16.
85. Vasudevan, S., Tong, Y., Steitz, J.A., Switching from repression to activation: microRNAs can up-regulate translation. Science 318 (2007), 1931–1934.
86. Vester, B., Wengel, J., LNA (locked nucleic acid): high-affinity targeting of complementary RNA and DNA. Biochemistry 43 (2004), 13233–13241.
87. Wang, X., Cao, L., Wang, Y., Wang, X., Liu, N., You, Y., Regulation of let-7 and its target oncogenes (review). Oncol. Lett. 3 (2012), 955–960.
88. Watashi, K., Yeung, M.L., Starost, M.F., Hosmane, R.S., Jeang, K.T., Identification of small molecules that suppress microRNA function and reverse tumorigenesis. J. Biol. Chem. 285 (2010), 24707–24716.
89. Wei, J.S., Song, Y.K., Durinck, S., Chen, Q.R., Cheuk, A.T., Tsang, P., Zhang, Q., Thiele, C.J., Slack, A., Shohet, J., Khan, J., The MYCN oncogene is a direct target of miR-34a. Oncogene 27 (2008), 5204–5213.
90. 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. 212 (2007), 285–292.
91. Yuan, T.L., Fellmann, C., Lee, C.S., Ritchie, C.D., Thapar, V., Lee, L.C., Hsu, D.J., Grace, D., Carver, J.O., Zuber, J., Luo, J., Mccormick, F., Lowe, S.W., Development of siRNA payloads to target KRAS-mutant cancer. Cancer Discov 4 (2014), 1182–1197.
92. Zhang, Y., Liu, D., Chen, X., Li, J., Li, L., Bian, Z., Sun, F., Lu, J., Yin, Y., Cai, X., Sun, Q., Wang, K., Ba, Y., Wang, Q., Wang, D., Yang, J., Liu, P., Xu, T., Yan, Q., Zhang, J., Zen, K., Zhang, C.Y., Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol. Cell 39 (2010), 133–144.
93. Zhang, X., Zuo, X., Yang, B., Li, Z., Xue, Y., Zhou, Y., Huang, J., Zhao, X., Zhou, J., Yan, Y., Zhang, H., Guo, P., Sun, H., Guo, L., Zhang, Y., Fu, X.D., MicroRNA directly enhances mitochondrial translation during muscle differentiation. Cell 158 (2014), 607–619.