MiRNA deregulation in cancer cells and the tumor microenvironment

Cancer Discovery

Volumn 6, Issue 3, 2016, Pages 235-246

  Rupaimoole, Rajesha ^a,b   Calin, George A ^a   Lopez Berestein, Gabriel ^a   Sood, Anil K ^a  

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

^b UNIVERSITY OF TEXAS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARGONAUTE 2 PROTEIN; EPHRIN RECEPTOR A2; EPHRIN RECEPTOR B2; EXPORTIN 5; HIGH MOBILITY GROUP A2 PROTEIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 6; MICRORNA; MICRORNA 155; MICRORNA 181A; MICRORNA 200; MICRORNA 21; MICRORNA 210; MICRORNA 214; MICRORNA 29; MICRORNA 506; NANOPARTICLE; RNA BINDING PROTEIN; SIRTUIN 1; STAT3 PROTEIN; SUPPRESSOR OF CYTOKINE SIGNALING 1; TOLL LIKE RECEPTOR 7; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR ELK 1; TRANSCRIPTION FACTOR TAP63; TRANSCRIPTION FACTOR TWIST; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6; UNCLASSIFIED DRUG;

A549 CELL LINE; BREAST CANCER; CANCER GROWTH; CELL INTERACTION; COLON CANCER; DOWN REGULATION; EPITHELIAL MESENCHYMAL TRANSITION; FIBROBLAST; GENE EXPRESSION REGULATION; GLIOBLASTOMA; HUMAN; HYPOXIA; IMMUNOMODULATION; INFLAMMATION; INTRACELLULAR SIGNALING; LIPOSOMAL GENE DELIVERY SYSTEM; METASTASIS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROTEIN PHOSPHORYLATION; REVIEW; T CELL LEUKEMIA; T LYMPHOCYTE ACTIVATION; TRANSCRIPTION REGULATION; TUMOR GROWTH; TUMOR MICROENVIRONMENT; ANIMAL; CELL TRANSFORMATION; DISEASE COURSE; GENE REGULATORY NETWORK; GENETICS; IMMUNOLOGY; METABOLISM; NEOPLASM; PATHOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; CELL TRANSFORMATION, NEOPLASTIC; DISEASE PROGRESSION; FIBROBLASTS; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE REGULATORY NETWORKS; HUMANS; HYPOXIA; INFLAMMATION; MICRORNAS; NEOPLASMS; SIGNAL TRANSDUCTION; TUMOR MICROENVIRONMENT;

EID: 84960096427     PISSN: 21598274     EISSN: 21598290     Source Type: Journal    
DOI: 10.1158/2159-8290.CD-15-0893     Document Type: Review

References (99)

1. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet 2011; 12: 861-74
2. 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: 843-54
3. 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; 75: 855-62
4. Spizzo R, Nicoloso MS, Croce CM, Calin GA. SnapShot: microRNAs in cancer. Cell 2009; 137: 586.e1
5. Boehm M, Slack FJ. MicroRNA control of lifespan and metabolism. Cell Cycle 2006; 5: 837-40
6. Pasquinelli AE, Hunter S, Bracht J. MicroRNAs: a developing story. Curr Opin Genet Dev 2005; 15: 200-5
7. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function . Cell 2004; 116: 281-97
8. 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; 96: 111-5
9. 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; 359: 2641-50
10. Garzon R, Calin GA, Croce CM. MicroRNAs in cancer. Annu Rev Med 2009; 60: 167-79
11. Ho JJ, Metcalf JL, Yan MS, Turgeon PJ, Wang JJ, Chalsev M, et al. Functional importance of Dicer protein in the adaptive cellular response to hypoxia. J Biol Chem 2012; 287: 29003-20
12. Shen J, Xia W, Khotskaya YB, Huo L, Nakanishi K, Lim SO, et al. EGFR modulates microRNA maturation in response to hypoxia through phosphorylation of AGO2. Nature 2013; 497: 383-7
13. Chen Z, Lai TC, Jan YH, Lin FM, Wang WC, Xiao H, et al. Hypoxiaresponsive miRNAs target argonaute 1 to promote angiogenesis. J Clin Invest 2013; 123: 1057-67
14. Rupaimoole R, Wu SY, Pradeep S, Ivan C, Pecot CV, Gharpure KM, et al. Hypoxia-mediated downregulation of miRNA biogenesis promotes tumour progression. Nat Commun 2014; 5
15. van den Beucken T, Koch E, Chu K, Rupaimoole R, Prickaerts P, Adriaens M, et al. Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER. Nat Commun 2014; 5: 5203
16. Huang X, Ding L, Bennewith KL, Tong RT, Welford SM, Ang KK, et al. Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation. Mol Cell 2009; 35: 856-67
17. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of posttranscriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 2008; 9: 102-14
18. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 2007; 449: 682-8
19. Allegra D, Bilan V, Garding A, Dohner H, Stilgenbauer S, Kuchenbauer F, et al. Defective DROSHA processing contributes to downregulation of MiR-15/-16 in chronic lymphocytic leukemia. Leukemia 2014; 28: 98-107
20. Dedes KJ, Natrajan R, Lambros MB, Geyer FC, Lopez-Garcia MA, Savage K, et al. Down-regulation of the miRNA master regulators Drosha and Dicer is associated with specific subgroups of breast cancer. Eur J Cancer 2011; 47: 138-50
21. Torres A, Torres K, Paszkowski T, Jodlowska-Jedrych B, Radomanski T, Ksiazek A, et al. Major regulators of microRNAs biogenesis Dicer and Drosha are down-regulated in endometrial cancer. Tumour Biol 2011; 32: 769-76
22. Eiring AM, Harb JG, Neviani P, Garton C, Oaks JJ, Spizzo R, et al. miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell 2010; 140: 652-65
23. Medina PP, Nolde M, Slack FJ. OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Nature 2010; 467: 86-90
24. Mutharasan RK, Nagpal V, Ichikawa Y, Ardehali H. microRNA-210 is upregulated in hypoxic cardiomyocytes through Akt- and p53- dependent pathways and exerts cytoprotective effects. Am J Physiol Heart Circ Physiol 2011; 301: H1519-30
25. Wei Y, Nazari-Jahantigh M, Chan L, Zhu M, Heyll K, Corbalan-Campos J, et al. The microRNA-342–5p fosters inflammatory macrophage activation through an Akt1- and microRNA-155-dependent pathway during atherosclerosis. Circulation 2013; 127: 1609-19
26. Xiang M, Birkbak NJ, Vafaizadeh V, Walker SR, Yeh JE, Liu S, et al. STAT3 induction of miR-146b forms a feedback loop to inhibit the NF-kappaB to IL-6 signaling axis and STAT3-driven cancer phenotypes . Sci Signal 2014; 7: ra11
27. 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; 131: 1109-23
28. Wang X, Zhao X, Gao P, Wu M. c-Myc modulates microRNA processing via the transcriptional regulation of Drosha. Sci Rep 2013; 3: 1942
29. Guo X, Liao Q, Chen P, Li X, Xiong W, Ma J, et al. The micro- RNA-processing enzymes: Drosha and Dicer can predict prognosis of nasopharyngeal carcinoma. J Cancer Res Clin Oncol 2012; 138: 49-56
30. Diaz-Garcia CV, Agudo-Lopez A, Perez C, Lopez-Martin JA, Rodriguez- Peralto JL, de Castro J, et al. DICER1, DROSHA and miRNAs in patients with non-small cell lung cancer: implications for outcomes and histologic classification. Carcinogenesis 2013; 34: 1031-8
31. Su X, Chakravarti D, Cho MS, Liu L, Gi YJ, Lin YL, et al. TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature 2010; 467: 986-90
32. Muller PA, Trinidad AG, Caswell PT, Norman JC, Vousden KH. Mutant p53 regulates Dicer through p63-dependent and -independent mechanisms to promote an invasive phenotype. J Biol Chem 2014; 289: 122-32
33. Martello G, Rosato A, Ferrari F, Manfrin A, Cordenonsi M, Dupont S, et al. A MicroRNA targeting dicer for metastasis control. Cell 2010; 141: 1195-207
34. Tokumaru S, Suzuki M, Yamada H, Nagino M, Takahashi T. let-7 regulates Dicer expression and constitutes a negative feedback loop. Carcinogenesis 2008; 29: 2073-7
35. Melo SA, Ropero S, Moutinho C, Aaltonen LA, Yamamoto H, Calin GA, et al. A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function. Nat Genet 2009; 41: 365-70
36. De Vito C, Riggi N, Cornaz S, Suva ML, Baumer K, Provero P, et al. A TARBP2-dependent miRNA expression profile underlies cancer stem cell properties and provides candidate therapeutic reagents in Ewing sarcoma. Cancer Cell 2012; 21: 807-21
37. Zhang X, Wan G, Berger FG, He X, Lu X. The ATM kinase induces microRNA biogenesis in the DNA damage response. Mol Cell 2011; 41: 371-83
38. Mori M, Triboulet R, Mohseni M, Schlegelmilch K, Shrestha K, Camargo FD, et al. Hippo signaling regulates microprocessor and links cell-density-dependent miRNA biogenesis to cancer. Cell 2014; 156: 893-906
39. 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: 303-15
40. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 2008; 10: 593-601
41. Korpal M, Lee ES, Hu G, Kang Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem 2008; 283: 14910-4
42. Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev 2008; 22: 894-907
43. Chan YC, Khanna S, Roy S, Sen CK. miR-200b targets Ets-1 and is down-regulated by hypoxia to induce angiogenic response of endothelial cells. J Biol Chem 2011; 286: 2047-56
44. Pecot CV, Rupaimoole R, Yang D, Akbani R, Ivan C, Lu C, et al. Tumour angiogenesis regulation by the miR-200 family. Nat Commun 2013; 4: 2427
45. Sung SY, Liao CH, Wu HP, Hsiao WC, Wu IH, Jinpu A, et al. Loss of let-7 microRNA upregulates IL-6 in bone marrow-derived mesenchymal stem cells triggering a reactive stromal response to prostate cancer. PloS One 2013; 8: e71637
46. 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; 67: 7713-22
47. Yang D, Sun Y, Hu L, Zheng H, Ji P, Pecot CV, et al. Integrated analyses identify a master microRNA regulatory network for the mesenchymal subtype in serous ovarian cancer. Cancer Cell 2013; 23: 186-99
48. 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: 828-33
49. Pickering MT, Stadler BM, Kowalik TF. miR-17 and miR-20a temper an E2F1-induced G1 checkpoint to regulate cell cycle progression. Oncogene 2009; 28: 140-5
50. Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, et al. MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 2008; 27: 2128-36
51. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH. Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem 2008; 283: 1026-33
52. Yan LX, Huang XF, Shao Q, Huang MY, Deng L, Wu QL, et al. Micro- RNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. Rna 2008; 14: 2348-60
53. Trabucchi M, Briata P, Garcia-Mayoral M, Haase AD, Filipowicz W, Ramos A, et al. The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. Nature 2009; 459: 1010-4
54. Schauer IG, Sood AK, Mok S, Liu J. Cancer-associated fibroblasts and their putative role in potentiating the initiation and development of epithelial ovarian cancer. Neoplasia 2011; 13: 393-405
55. Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer 2006; 6: 392-401
56. Bronisz A, Godlewski J, Wallace JA, Merchant AS, Nowicki MO, Mathsyaraja H, et al. Reprogramming of the tumour microenvironment by stromal PTEN-regulated miR-320. Nat Cell Biol 2012; 14: 159-67
57. Du R, Sun W, Xia L, Zhao A, Yu Y, Zhao L, et al. Hypoxia-induced down-regulation of microRNA-34a promotes EMT by targeting the Notch signaling pathway in tubular epithelial cells. PloS One 2012; 7: e30771
58. Mitra AK, Zillhardt M, Hua Y, Tiwari P, Murmann AE, Peter M E, et al. MicroRNAs reprogram normal fibroblasts into cancer-associated fibroblasts in ovarian cancer. Cancer Discov 2012; 2: 1100-8
59. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420: 860-7
60. Tili E, Michaille JJ, Croce CM. MicroRNAs play a central role in molecular dysfunctions linking inflammation with cancer. Immunol Rev 2013; 253: 167-84
61. Iliopoulos D, Hirsch HA, Struhl K. An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 2009; 139: 693-706
62. Taganov KD, Boldin MP, Chang KJ, Baltimore D. NF-kappaBdependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A 2006; 103: 12481-6
63. O’Connell RM, Chaudhuri AA, Rao DS, Baltimore D. Inositol phosphatase SHIP1 is a primary target of miR-155. Proc Natl Acad Sci U S A 2009; 106: 7113-8
64. Tili E, Michaille JJ, Wernicke D, Alder H, Costinean S, Volinia S, et al. Mutator activity induced by microRNA-155 (miR-155) links inflammation and cancer. Proc Natl Acad Sci U S A 2011; 108: 4908-13
65. Dudda JC, Salaun B, Ji Y, Palmer DC, Monnot GC, Merck E, et al. MicroRNA-155 is required for effector CD8+ T cell responses to virus infection and cancer. Immunity 2013; 38: 742-53
66. Li QJ, Chau J, Ebert PJ, Sylvester G, Min H, Liu G, et al. miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 2007; 129: 147-61
67. Yamagishi M, Nakano K, Miyake A, Yamochi T, Kagami Y, Tsutsumi A, et al. Polycomb-mediated loss of miR-31 activates NIK-dependent NF-kappaB pathway in adult T cell leukemia and other cancers. Cancer Cell 2012; 21: 121-35
68. Kulshreshtha R, Ferracin M, Wojcik SE, Garzon R, Alder H, Agosto- Perez FJ, et al. A microRNA signature of hypoxia. Mol Cell Biol 2007; 27: 1859-67
69. Wang H, Flach H, Onizawa M, Wei L, McManus MT, Weiss A. Negative regulation of Hif1a expression and TH17 differentiation by the hypoxia-regulated microRNA miR-210. Nat Immunol 2014; 15: 393-401
70. Li Q, Zhang D, Wang Y, Sun P, Hou X, Larner J, et al. MiR-21/Smad 7 signaling determines TGF-beta1-induced CAF formation. Sci Rep 2013; 3: 2038
71. Fabbri M, Paone A, Calore F, Galli R, Gaudio E, Santhanam R, et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci U S A 2012; 109: E2110-6
72. O’Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A 2007; 104: 1604-9
73. Squadrito ML, Pucci F, Magri L, Moi D, Gilfillan GD, Ranghetti A, et al. miR-511–3p modulates genetic programs of tumor-associated macrophages. Cell Rep 2012; 1: 141-54
74. Min S, Li L, Zhang M, Zhang Y, Liang X, Xie Y, et al. TGF-betaassociated miR-27a inhibits dendritic cell-mediated differentiation of Th1 and Th17 cells by TAB3, p38 MAPK, MAP2K4 and MAP2K7. Gen Immun 2012; 13: 621-31
75. Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev 2007; 26: 225-39
76. Keith B, Simon MC. Hypoxia-inducible factors, stem cells, and cancer. Cell 2007; 129: 465-72
77. Chen S, Xue Y, Wu X, Le C, Bhutkar A, Bell EL, et al. Global microRNA depletion suppresses tumor angiogenesis. Genes Dev 2014; 28: 1054-67
78. Wu C, So J, Davis-Dusenbery BN, Qi HH, Bloch DB, Shi Y, et al. Hypoxia potentiates microRNA-mediated gene silencing through posttranslational modification of Argonaute2. Mol Cell Biol 2011; 31: 4760-74
79. Puissegur MP, Mazure NM, Bertero T, Pradelli L, Grosso S, Robbe-Sermesant K, et al. miR-210 is overexpressed in late stages of lung cancer and mediates mitochondrial alterations associated with modulation of HIF-1 activity. Cell Death Differ 2011; 18: 465-78
80. Qi J, Qiao Y, Wang P, Li S, Zhao W, Gao C. microRNA-210 negatively regulates LPS-induced production of proinflammatory cytokines by targeting NF-kappaB1 in murine macrophages. FEBS Lett 2012; 586: 1201-7
81. Kopriva SE, Chiasson VL, Mitchell BM, Chatterjee P. TLR3-induced placental miR-210 down-regulates the STAT6/interleukin-4 pathway. PloS One 2013; 8: e67760
82. 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: 211–5
83. Rokavec M, Oner MG, Li H, Jackstadt R, Jiang L, Lodygin D, et al. IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis. J Clin Invest 2014; 124: 1853-67
84. 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: 5184-93
85. el Azzouzi H, Leptidis S, Dirkx E, Hoeks J, van Bree B, Brand K, et al. The hypoxia-inducible microRNA cluster miR-199a approximately 214 targets myocardial PPARdelta and impairs mitochondrial fatty acid oxidation. Cell Metabol 2013; 18: 341-54
86. Joshi HP, Subramanian IV, Schnettler EK, Ghosh G, Rupaimoole R, Evans C, et al. Dynamin 2 along with microRNA-199a reciprocally regulate hypoxia-inducible factors and ovarian cancer metastasis. Proc Natl Acad Sci U S A 2014; 111: 5331-6
87. Cheng CJ, Saltzman WM, Slack FJ. Canonical and non-canonical barriers facing antimiR cancer therapeutics. Curr Med Chem 2013; 20: 3582-93
88. Rupaimoole R, Han HD, Lopez-Berestein G, Sood AK. MicroRNA therapeutics: principles, expectations, and challenges. Chinese J Cancer 2011; 30: 368-70
89. Pecot CV, Calin GA, Coleman RL, Lopez-Berestein G, Sood AK. RNA interference in the clinic: challenges and future directions. Nat Rev Cancer 2011; 11: 59-67
90. Ling H, Fabbri M, Calin GA. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov 2013; 12: 847-65
91. 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; 19: 1116-22
92. Bader AG. miR-34 - a microRNA replacement therapy is headed to the clinic. Front Genet 2012; 3: 120
93. Nishimura M, Jung EJ, Shah MY, Lu C, Spizzo R, Shimizu M, et al. Therapeutic synergy between microRNA and siRNA in ovarian cancer treatment. Cancer Discov 2013; 3: 1302-15
94. 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; 65: 6910-8
95. Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med 2013; 368: 1685-94
96. Zheng D, Giljohann DA, Chen DL, Massich MD, Wang XQ, Iordanov H, et al. Topical delivery of siRNA-based spherical nucleic acid nanoparticle conjugates for gene regulation. Proc Natl Acad Sci U S A 2012; 109: 11975–80
97. Jensen SA, Day ES, Ko CH, Hurley LA, Luciano JP, Kouri FM, et al. Spherical nucleic acid nanoparticle conjugates as an RNAi-based therapy for glioblastoma. Sci Transl Med 2013; 5: 209ra152
98. Ibrahim AF, Weirauch U, Thomas M, Grunweller A, Hartmann RK, Aigner A. MicroRNA replacement therapy for miR-145 and miR-33a is efficacious in a model of colon carcinoma. Cancer Res 2011; 71: 5214-24
99. Kota J, Chivukula RR, O’Donnell KA, Wentzel EA, Montgomery CL, Hwang HW, et al. Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 2009; 137: 1005-17.