MicroRNA biogenesis pathway as a therapeutic target for human disease and cancer

Current Pharmaceutical Design

Volumn 19, Issue 4, 2013, Pages 745-764

  de Santa, Francesca ^a,c   Iosue, Ilaria ^a   Del Rio, Alberto ^b   Fazi, Francesco ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b UNIVERSITY OF BOLOGNA   (Italy)

^c CNR   (Italy)

Author keywords

Argonaute proteins; Crystallography; Dicer; Drosha; Exportin 5; MicroRNA; NMR; RNA based drugs and therapies; Small molecules design

Indexed keywords

MICRORNA; MICRORNA 10B; MICRORNA 122; MICRORNA 126; MICRORNA 143; MICRORNA 145; MICRORNA 155; MICRORNA 200; MICRORNA 21; MICRORNA 26A; MICRORNA 29; MICRORNA 31; MICRORNA 34A; RNA BINDING PROTEIN;

3' UNTRANSLATED REGION; ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; B CELL LYMPHOMA; BLADDER CANCER; BREAST CANCER; BURKITT LYMPHOMA; CANCER STEM CELL; CARDIOVASCULAR DISEASE; COLON CANCER; COLORECTAL CARCINOMA; CONGESTIVE CARDIOMYOPATHY; DIGESTIVE SYSTEM CANCER; DISEASE COURSE; GENETIC ASSOCIATION; GENOMIC INSTABILITY; HODGKIN DISEASE; HUMAN; LEUKEMIA; LUNG CANCER; MYELOMA; NEOPLASM; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN STABILITY; REVIEW; RNA INTERFERENCE; STOMACH CANCER;

EID: 84876729023     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161213804581846     Document Type: Review

References (244)

1. de Fourgerolles A, Vornlocher HP, Maraganore J, et al. Interfering with disease: a progress report on siRNA-based therapeutics. Nat Rev Drug Discov 2007; 6: 443-53.
2. Kasinski AL, Slack FJ. Epigenetics and genetics. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer 2011; 11: 849-64.
3. Fazi F. Nervi C. MicroRNA: basic mechanisms and transcriptional regulatory networks for cell fate determination. Cardiovasc Res 2008; 79: 553-61.
4. Bartel, DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281-297.
5. Zeng Y. Principles of micro-RNA production and maturation. Oncogene 2006; 25: 6156-6162.
6. Ambros V. The functions of animal microRNAs. Nature. 2004; 431:350-5.
7. Xu P, Guo M, Hay BA. MicroRNA and the regulation of cell death. Trends Genet 2004; 20:617-624.
8. Chen CZ, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science 2004; 303: 83-86.
9. Hatfield SD, Shcherbata HR, Fischer KA, et al. Stem cell division is regulated by the mocroRNA pathway. Nature 2005; 435: 974-978.
10. Cimmino A, Calin GA, Fabbri M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci 2005;102: 13944-13949.
11. Agami R. microRNAs, RNA binding proteins and cancer. Eur J Clin Invest 2010; 40: 370-4.
12. Kedde M, Agami R. Interplay between microRNAs and RNAbinding proteins determines developmental processes. Cell cycle 2008; 7: 899-903.
13. Kim VN, Han J, Siomi MC. Biogenesis of 3βUTRs contain fewer miRNA binding small RNAs in animals. Nat Rev Mol Cell Biol 2009;10:126-39.
14. Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ. Processing of primary microRNAs by the Microprocessor complex. Nature 2004; 432: 231-35.
15. Gregory RI. The Microprocessor complex mediates the genesis of microRNAs. Nature 2004; 432: 235-40.
16. Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 2003; 17: 3011-3016.
17. Lund E, Güttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science 2004; 303: 95-98.
18. Hutvágner G, McLachlan J, Pasquinelli AE, et al. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science 2001; 293: 834-838.
19. Chendrimada TP, Gregory RI, Kumaraswamy E, et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 2005; 436: 740-44.
20. Peters L, Meister G. Argonaute proteins: mediators of RNA silencing. Mol Cell 2007; 26: 611-23.
21. Diederichs S, Haber DA. Dual role for argonautes in microRNA processing and posttranscriptional regulation of microRNA expression. Cell 2007; 131: 1097-108.
22. Eulalio A, Huntzinger E, Izaurralde E. GW182 interaction with Argonaute is essential for miRNA-mediated translational repression and mRNA decay. Nat Struct Mol Biol 2008; 15: 346-53.
23. Selbach M, Schwanhausser B, Thierfelder N, et al. Widespread changes in protein synthesis induced by microRNAs. Nature 2008; 455: 58-63.
24. Pillai RS, Bhattacharyya SN, Artus CG, et al. Inhibition of translational initiation by miRNAs represent critical regulators of Let-7 microRNA in human cells. Science 2005; 309: 1573-6.
25. Humphreys DT, Westman BJ, Martin DI, Preiss T. MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function. Proc Natl Acad Sci U S A 2005; 102: 16961-6.
26. Petersen CP, Bordeleau ME, Pelletier J, Sharp PA. Short RNAs repress translation after initiation mammalian cells. Mol Cell 2006; 21: 533-42.
27. Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 2009; 19: 92-105.
28. Baek D, Villen J, Shin C, et al. The impact of microRNAs on protein output. Nature 2008; 455: 64-71.
29. Wu W, Sun M, Zuo GM, Chen J. MicroRNA and cancer: current status and prospective. Int J Cancer 2006; 120: 953-960.
30. Medell JT. MicroRNAs: critical regulators of development, cellular physiology and malignancy. Cell Cycle 2005; 4: 1179-1184.
31. Kent OA, Mendell JT. A small piece in the cancer puzzle: microRNA as tumor suppressors and oncogene. Oncogene 2006; 25: 6188-6196.
32. Hummond SM. MicroRNA as oncogenes. Curr Opin Genet Deve 2006; 16: 4-9.
33. Esequela-Kercher A, Slack FJ. Oncomir-microRNA with a role in cancer. Nat Rev Cancer 2006; 6: 259-269.
34. Calin GA, Croce CM. MicroRNA and chromosomal abnormalities in cancer cells. Oncogene 2006; 25: 6202-6210.
35. Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature 2005; 435: 834-8.
36. Lujambio A, Calin, G A, Villanueva A, et al. A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA 2008; 105: 13556-13561.
37. Lujambio A, Ropero S, Ballestar E, et al. Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res 2007; 67: 1424-1429.
38. Makunin IV, Pheasant M, Simons, C, et al. Orthologous microRNA genes are located in cancer-associated genomic regions in human and mouse. PLoS One 2007; 2: e1133.
39. Xi Y, Shalgi R, Fodstad O, Pilpel Y, Ju J. Differentially regulated micro-RNAs and actively translated messenger RNA transcripts by tumor supppressor p53 in colon cancer. Clin Cancer Res 2006; 12: 2014-24.
40. O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2005; 435: 839-43.
41. Lee EJ, Baek M, Gusev Y, Brackett DJ, Nuovo GJ, Schmittgen TD. Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors. RNA 2008; 14: 35-42.
42. Mishra PJ, Banerjee D, Bertino JR. MiRSNPs or MiRpolymorphisms, new players in microRNA mediated regulation of the cell: Introducing microRNA pharmacogenomics. Cell Cycle 2008; 7: 853-8.
43. Lima RT, Busacca S, Almeida GM, et al. MicroRNA regulation of core apoptosis pathways in cancer. Eur J Cancer 2011; 47: 163-74.
44. Negrini M, Nicoloso MS, Calin GA. MicroRNAs and cancer-new paradigms in molecular oncology. Curr Opin Cell Biol 2009; 21: 470-479.
45. Urbich C, Kuehbacher A, Dimmeler S. Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovasc Res 2008; 79: 581-588.
46. Gregory PA, Bracken CP, Bert AG, Goodall G.J. MicroRNAs as regulators of epithelial-mesenchymal transition. Cell Cycle 2008; 7: 3112-3118.
47. Nicoloso MS, Spizzo R, Shimizu M, Rossi S, Calin GA. MicroRNAs-the micro steering wheel of tumour metastases. Nature Rev Cancer 2009; 9: 293-302.
48. Olson P, Lu J, Zhang H, et al. MicroRNA dynamics in the stages of tumorigenesis correlate with hallmark capabilities of cancer. Genes Dev 2009; 23: 2152-2165.
49. Chen J, Odenike O, Rowley JD. Leukaemogenesis: more than mutant genes. Nat Rev Cancer 2010; 10: 23-6.
50. Ono K, Kuwabara Y, Han J. microRNAs and cardiovascular diseases. FEBS J 2011; 278: 1619-33.
51. Guller I, Russell A P. MicroRNAs in skeletal muscle: their role and regulation in development, disease and function. J Physiol 2010; 588.21: 4075-4087
52. Saugstad JA. MicroRNAs as effectors of brain function with roles in ischemia and injury, neuroprotecion, and neurodegeneration. J Cereb Blood Flow Metab 2010; 30: 1564-76.
53. Kerr TA, Korenblat KM, Davidson NO. MicroRNAs and liver disease. Transl Res 2011; 157: 241-52.
54. Li JY, Yong TY, Michael MZ, et al. Review: the role of microRNAs in kidney disease. Nephrology 2010; 15: 599-608.
55. Heneghan HM, Miller N, Kerin MJ. Role of microRNAs in obesity and the metabolic syndrome. Obes Rev 2010; 11: 354-61
56. Ferland-McCollough D, Ozanne SE, Siddle K, et al. The involvement of microRNAs in type 2 diabetes. Biochem Soc Trans 2010; 38: 1565-70.
57. Bravo JA, Dinan TG. MicroRNAs: a nvel therapeutic target for schizophrenia. Curr Pharm Des 2011; 17: 176-88.
58. Fiore R, Schratt G. microRNAs in synapse development: tiny molecules to remember. Expert Opin Biol Ther. 2007; 7: 1823-31.
59. Sonkoly E, Ståhle M, Pivarcsi A, et al. MicroRNAs: novel regulators in skin inflammation. Clin Exp Dermatol 2008; 33: 312-5.
60. Hill JA, Olson EN. Cardiac plasticity. N Engl J Med 2008; 358: 1370-80.
61. Carè A, Catalucci D, Felicetti F, et al. MicroRNA-133 controls cardiac hypertrophy. Nat Med 2007; 13: 613-8.
62. Van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 2007; 316: 575-9.
63. Bonauer A, Carmona G, Iwasaki M, et al. MicroRA-92a controls angiogenesis and functional recovery of ischemic tiissues in mice. Science 2009; 324: 1710-3.
64. Rao PK, Toyama Y, Chiang HR, et al. Loss of cardiac microRNAmediated regulation leads to dilated cardiomyopathy and heart failure. Circ Res 2009; 105: 585-94.
65. Van Rooij E, Sutherland LB, Thatcher JE, et al. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci USA 2008; 105: 13027-32.
66. Naga Prasad SV, Duan ZH, Gupta MK, et al. Unique microRNA profile in end-stage heart failure indicates alterations in specific cardiovascular signaling networks. J Biol Chem 2009; 284: 27487-99.
67. Gupta SK, Bang C, Thum T. Circulating microRNAs as biomarkers and potential paracrine mediators of cardiovascular disease. Circ Cardiovasc Genet 2010; 3: 484-8.
68. Akao Y, Nakagawa Y, Naoe T, et al. Let-7 microRNA functions as a potential growth suppressor in human colon cancer cells. Biol Pharm Bull 2006; 29: 903-6.
69. Bonci D, Coppola V, Musumeci M, et al. The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med 2008; 14: 1271-7.
70. Xiong Y, Fang JH, Yun JP, et al. Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hapatocellular carcinoma. Hepatology 2010; 51: 836-45.
71. Davidson BL, McCray PB Jr, et al. Current prospects for RNA interference-based therapies. Nat Rev Genet 2011; 12: 329-40.
72. Michelfelder S, Trepel M. Adeno-associated viral vectors and their redirection to cell-type specific receptors. Adv Genet 2009; 67: 29-60.
73. Krützfeldt J, Rajewsky N, Braich R, et al. Silencing of microRNAs in vivo with "antagomirs". Nature 2005; 438: 685-9.
74. Krützfeldt J, Kuwajima S, Braich R, et al. specificity, duplex degradation and subcellular localization of antagomirs. Nucleic Acids Res 2007; 35: 2885-92.
75. Vester B, Wengel J. LNA (locked nucleic acid): high-affinity targeting of complementary RNA and DNA. Biochemistry 2004; 43: 13233-41.
76. Elmén J, Lindow M, Silahtaroglu A, et al. Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to upregulation of a large set of predicted mRNAs in the liver. Nucleic Acids Res 2008; 36: 1153-62.
77. Ebert MS, Neilson JR, Sharp PA, et al. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 2007; 4: 721-6.
78. Ebert MS, Sharp PA. MicroRNA sponges: progress and possibilities. RNA 2010; 16: 2043-50.
79. Loya CM, Lu CS, Van Vactor D, Fulga TA. Transgenic microRNA inhibition with spatiotemporal specificity in intact organisms. Nat Methods 2009; 6: 897-903.
80. Brown BD, Naldini L. Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications. Nat Rev Genet 2009; 10: 578-85.
81. Fabani MM, Abreu-Goodger C, Williams D, et al. Efficient inhibition of miR-155 function in vivo by peptide nucleic acids. Nucleic Acids Re. 2010; 38: 4466-75.
82. Torres AG, Fabani MM, Vigorito E, et al. Chemical structure requirements and cellular targeting of microRNA-122 by peptide nucleic acids anti-miRs. Nucleic Acids Res. 2011; Nov 8.
83. Yan LX, Wu QN, Zhang Y, et al. Knockdown of miR-21 in human breast cancer cell lines inhibits proliferation, in vivo migration and in vivo tumor growth. Breast Cancer Res 2011; 13: R2.
84. Song E, Lee SK, Wang J, et al. RNA interference targeting Fas protects mice from fulminant hepatitis. Nat Med 2003; 9: 347-51.
85. De Paula D, Bentley MV, Mahato RI, et al. Hydrophobization and bioconjugation for enhanced siRNA delivery and targeting. RNA 2007; 13: 431-56.
86. Zuhorn IS, Engberts JB, Hoekstra D. Gene delivery by cationic lipid vectors: overcoming cellular barriers. Eur Biophys J 2007; 36: 349-62.
87. Rosi NL, Giljohann DA, Thaxton CS, et al. oligonucleotidemodified gold nanoparticles for intracellular gene regulation. Science 2006; 312: 1027-30.
88. Chen Y, Zhu X, Zhang X, et al. Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy. Mol Ther 2010; 18: 1650-6.
89. Davidson B L and McCray Jr. P B. Current prospects for RNA interference-based therapies. Nature Reviews Genetics 2011; 12: 329-340
90. Fabbri E, Brognara E, Borgatti M, et al. miRNA therapeutics: delivery and biological activity of peptide nucleic acids targeting miRNAs. Epigenomics 2011; 3: 733-45.
91. Macadangdang B, Zhang N, Lund PE, et al. Inhibition of multidrug resistance by SV40 pseudovirion delivery of an antigene peptide nucleic acid (PNA) in cultured cells. Plos One 2011; 6: e17981
92. Elmén J, Lindow M, Schütz S, et al. LNA-mediated microRNA silencing in non-human primates, Nature 2008; 452: 896-9.
93. Lanford RE, Hildebrandt-Eriksen ES, Petri A, et al. Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 2010; 327: 198-201.
94. Bai S, Nasser MW, Wang B, et al. MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. J Biol Chem 2009; 284: 32015-27.
95. Burchard J, Zhang C, Liu AM, et al. MicroRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma. Mol Syst Biol 2010; 6: 402.
96. Tsai WC, Hsu PW, Lai TC, et al. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology 2009; 49: 1571-82.
97. Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 2005; 65: 6029-33.
98. Gabriely G, Wurdinger T, Kesari S, et al. MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators. Mol Cell Biol 2008; 28: 5369-80.
99. Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY. MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res 2008; 18: 350-9
100. Zheng J, Xue H, Wang T, Jiang Y, Liu B, Li J, et al. miR-21 downregulates the tumor suppressor P12 CDK2AP1 and stimulates cell proliferation and invasion. J Cell Biochem 2011; 112: 872-80.
101. Hatley ME, Patrick DM, Garcia MR, et al. Modulation of K-Rasdependent lung tumorigenesis by MicroRNA-21. Cancer Cell 2010; 18: 282-93.
102. Ma X, Kumar M, Choudhury SN, Becker Buscaglia LE, et al. Loss of the miR-21 allele elevates of its target genes and reduces tumorigenesis. Proc Natl Acad Sci U S A 2011; 108: 10144-9.
103. 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.
104. Reinhart BJ, Slack FJ, Basson M, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 2000; 403: 901-6.
105. Calin GA, Sevignani C, Dumitru CD, et al. Human microRNA genes frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 2004; 101: 2999-3004.
106. Lee YS, Dutta A. The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev 2007; 21: 1025-30.
107. Mayr C, Hemann MT, Bartel DP. Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science 2007; 315: 1576-9.
108. Sampson VB, Rong NH, Han J, et al. MicroRNA let-7a downregulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res 2007; 67: 9762-70.
109. Johnson CD, Esquela-Kerscher A, Stefani G, et al. The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res 2007; 67: 7713-22.
110. Johnson SM, Grosshans H, Shingara J, et al. RAS is regulated by the let-7 microRNA family. Cell 2005; 120: 635-647.
111. Takamizawa J, Konishi H, Yanagisawa K, et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 2004; 64: 3753-756.
112. van Jaarsveld MT, Helleman J, Berns EM, Wiemer EA. MicroRNAs in ovarian cancer biology and therapy resistance. Int J Biochem Cell Biol 2010; 42: 1282-90.
113. Yu F, Yao H, Zhu P, et al. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 2007; 131: 1109-23.
114. Esquela-Kerscher A, Trang P, Wiggins JF, et al. The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle 2008; 7: 759-64.
115. Kumar MS, Erkeland SJ, Pester RE, et al. Suppression of nonsmall cell lung tumor development by the let-7 microRNA family. Proc Natl Acad Sci U S A 2008; 105: 3903-8.
116. Trang P, Medina PP, Wiggins JF, et al. Regression of murine lung tumors by the let-7 microRNA. Oncogene 2010; 29: 1580-7.
117. Trang P, Wiggins JF, Daige CL, 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
118. Lee ST, Chu K, Oh HJ, et al. Let-7 microRNA inhibits the proliferation of human glioblastoma cells. J Neurooncol 2011; 102: 19-24.
119. Wiggins JF, Ruffino L, Kelnar K, et al. Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res 2010; 70: 5923-30
120. Liu C, Kelnar K, Liu B, et al. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nature Med 2011; 17: 211-215
121. Pramanik D, Campbell NR, Karikari C, et al. Restitution of tumor suppressor microRNAs using a systemic nanovector inhibits pancreatic cancer growth in mice. Mol Cancer Ther 2011; 10: 1470-80.
122. Zhang X, Liu S, Hu T, He Y, Sun S. Up-regulated microRNA-143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression. Hepatology 2009; 50: 490-499.
123. Kota J, Chivukula RR, O'Donnell KA, et al. Therapeutic microRNA delivery suppress tumorigenesis in a murine liver cancer model. Cell 2009; 137: 1005-17.
124. Mavrakis KJ, Van Der Meulen J, Wolfe AL, et al. A cooperative microRNA-tumor suppressor gene network in acute T-cell lymphoblastic leukemia (T-ALL). Nat Genet 2011; 43: 673-8.
125. Baffa R, Fassan M, Volinia S, et al. MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol 2009; 219: 214-21.
126. Ma L, Reinhardt F, Pan E, et al. Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol 2010; 28: 341-7.
127. Bloomston M, Frankel WL, Petrocca F, et al. MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis. JAMA 2007; 297: 1901-8
128. Tan HX, Wang Q, Chen LZ, et al. MicroRNA-9 reduces cell invasion and E-cadherin secretion in SK-Hep-1 cell. Med Oncol 2010; 27: 654-60
129. Ciafre SA, Galardi S, Mangiola A, et al. Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun 2005; 334: 1351-8
130. Gabriely G, Yi M, Narayan RS, et al. Human glioma growth is controlled by micro-RNA-10b. Cancer Res 2011; 71: 3563-72.
131. Anand S, Cheresh DA. MicroRNA-mediated regulation of the angiogenic switch. Curr Opin Hematol 2011; 18: 171-6.
132. Anand S, Majeti BK, Acevedo LM, et al. MicroRNA-132-mediated loss of p120RasGAP acti vates the endothelium to facilitate pathological angiogenesis. Nat Med 2010; 16: 909-14.
133. Fabbri M, Garzon R, Cimmino A, 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: 15805-10.
134. Zhao JJ, Lin J, Lwin T, et al. MicroRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma. Blood 2010; 115: 2630-9.
135. Garzon R, Heaphy CE, Havelange V, et al. MicroRNA 29b functions in acute myeloid leukemia. Blood 2009; 114: 5331-41.
136. Pekarsky Y, Croce CM. Is miR-29 an oncogene or tumor suppressor in CLL? Oncotarget 2010; 1: 224-7.
137. Mott JL, Kobayashi S, Bronk SF, Gores GJ. Mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene 2007; 26: 6133-40.
138. Han YC, Park CY, Bhagat G, et al. microRNA-29a induces aberrant self-renewal capacity in hematopoietic progenitors, biased myeloid development, and acute myeloid leukemia. J Exp Med 2010; 207: 475-89.
139. Gebeshulber CA, Zatloukal K, Martinez J. miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis. EMBO Rep 2009; 10: 400-5.
140. Santanam U, Zanesi N, Efanov A, et al. Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression. Proc Natl Acad Sci USA 2010; 107: 12210-5.
141. Yang B, Lin H, Xiao J, et al. The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat Med 2007; 13: 486-91.
142. Ikeda S, He A, Kong SW, et al. MicroRNA-1 negatively regulates expression of the hypertrophy-associated calmodulin and Mef2a genes. Mol Cell Biol 2009; 29: 2193-204
143. Elia L, Contu R, Quintavalle M, et al. Reciprocal regulation of microRNA-1 and insulin-like growth factor-1 signal transduction cascade in cardiac and skeletal muscle in physiological and pathological conditions. Circulation 2009; 120: 2377-85.
144. Tang Y, Zheng J, Sun Y, Wu Z, Liu Z, Huang G. MicroRNA-1 regulates cardiomyocyte apoptosis by targeting Bcl-2. Int Heart J 2009; 50: 377-87.
145. Li Q, Song XW, Zou J, et al. Attenuation of microRNA-1 derepresses the cytoskeleton regulatory protein twinfilin-1 to provoke cardiac hypertrophy. J Cell Sci 2010; 123: 2444-52.
146. Callis TE, Pandya K, Seok HY, et al. MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Invest. 2009 Sep;119(9):2772-86.
147. van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 2007; 316: 575-9.
148. Montgomery RL, Hullinger TG, Semus HM, et al. Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure. Circulation 2011; 124: 1537-47.
149. da Costa Martins PA, Salic K, Gladka MM, et al. MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signalling. Nat Cell Biol 2010; 12: 1220-7.
150. Thum T, Gross C, Fiedler J, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 2008; 456: 980-4.
151. Roy S, Khanna S, Hussain SR MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue. Cardiovasc Res 2009; 82: 21-9.
152. Patrick DM, Montgomery RL, Qi X, et al. Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice. J Clin Invest 2010; 120: 3912-6.
153. Thum T, Chau N, Bhat B, et al. Comparison of different miR-21 inhibitor chemistries in a cardiac disease model. J Clin Invest 2011; 121: 461-2.
154. Liu G, Friggeri A, Yang Y, et al. MiR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis. J Exp Med 2010; 207: 1589-97.
155. Zhong X, Chung AC, Chen HY, Meng XM, Lan HY. Smad3-mediated upregulation of miR-21 promotes renal fibrosis. J Am Soc Nephrol 2011; 22: 1668-81.
156. van Kouwenhove M, Kedde M, Agami R. MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Cancer 2011; 11: 644-56.
157. Davis BN, Hata A. microRNA in Cancer: The involvement of aberrant microRNA biogenesis regulatory pathways. Genes Cancer 2010; 1: 1100-1114.
158. Shiohama A, Sasaki T, Noda S, Minoshima S, Shimizu N. Molecular cloning and expression analysis of a novel gene DGCR8 located in the DiGeorge syndrome chromosomal region. Biochem Biophys Res Commun 2003; 304: 184-90.
159. Sand M, Skrygan M, Georgas D, et al. Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA-induced silencing complex (RISC) components Argonaute-1, Argonaute-2, PACT, TARBP1, and TARBP2 in epithelial skin cancer. Mol Carcinog 2011, Oct 24.
160. Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet 2007; 39: 673-7.
161. Merritt WM, Lin YG, Han LY, et al. Dicer, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med 2008; 359: 2641-50.
162. Sugito N, Ishiguro H, Kuwabara Y, et al. RNASEN regulates cell proliferation and affects serviva in esophageal cancer patients. Clin Cancer Res 2006; 12: 7322-8.
163. Dedes KJ, Natrajan R, Lambros MB, 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.
164. Fuller-Pace FV, Moore HC. RNA helicase p68 and p72: multifunctional proteins with important implications for cancer development. Future Oncol 2011; 7: 239-51.
165. Suzuki HI, Yamagata K, Sugimoto K, Iwamoto T, Kato S, Miyazono K. Modulation of microRNA processing by p53. Nature 2009; 460: 529-33.
166. Lee EJ, Baek M, Gusev Y, Brackett DJ, Nuovo GJ, Schmittgen TD. Systematic evaluation of microRNA processing patterns in tissues, cell lines, and tumors. RNA 2008; 14: 35-42.
167. Melo SA, Esteller M. A precursor microRNA in a cancer cell nucleus: get me out of here! Cell cycle 2011; 10: 922-5.
168. Melo SA, Moutinho C, Ropero S, et al. A genetic defect in exportin-5 traps precursor microRNAs in the nucleus of cancer cells. Cancer Cell 2010; 18: 303-15.
169. Zhang L, Huang J, Yang N, et al. microRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci U S A 2008; 103: 9136-41.
170. Karube Y, Tanaka H, Osada H, et al. Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci 2005; 96: 111-5.
171. Chiosea S, Jelezcova E, Chandran U, et al. Up-regulation of dicer, a component of the MicroRNA machinery, in prostate adenocarcinoma. Am J Pathol 2006; 169: 1812-1820.
172. Chiosea S, Jelezcova E, Chandran U, et al. Overexpression of Dicer in precursor lesions of lung adenocarcinoma. Cancer Res 2007; 67: 2345-2350.
173. Heravi-Moussavi A, Anglesio MS, Cheng SW, et al. Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers. N Engl J Med 2012; 366: 234-42.
174. Bu Y, Lu C, Bian C, et al. Knockdown of Dicer in MCF-7 human breast carcinoma cells results in G1 arrest and increased sensitivity to cisplatin. Oncol Rep 2009; 21: 13-7.
175. Han L, Zhang A, Zhou X, et al. Downregulation of Dicer enhances tumor cell proliferation and invasion. Int J Oncol 2010; 37: 299-305.
176. Kumar MS, Pester RE, Chen CY, et al. Dicer1 functions as haploinsufficient tumor suppressor. Genes Dev 2009; 23: 2700-4.
177. Su X, Chakravarti D, Cho MS, et al. TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. Nature 2010; 467: 986-90.
178. Lambertz I, Nittner D, Mestdagh P, et al. Monoallelic but not biallelic loss of Dicer1 promotes tumorigenesis in vivo. Cell Death Differ 2010; 17: 633-41.
179. Martello G, Rosato A, Ferrari F, et al. A MicroRNA targeting dicer for metastasis control. Cell 2010; 141: 1195-207.
180. Ting AH, Suzuki H, Cope L, et al. A requirement for DICER to maintain full promoter CpG island hypermethylation in human cancer cells. Cancer Res 2008; 68: 2570-5.
181. Andreoli F, Barbosa AJM, Parenti MD, Del Rio A. Modulation of epigenetic targets for anticancer therapy: clinicopathological relevance, structural data and drug discovery perspectives. Curr Pharm Des 2013; 19(4): 578-613.
182. Melo SA, Ropero S, Moutinho C, et al. A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function. Nat Genet 2009; 41: 365-70.
183. Carmell MA, Xuan Z, Zhang MQ, Hannon GJ. The Argonaute family: tentarle that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis. Genes Dev 2002; 16: 2733-42.
184. Nelson P, Kiriakidou M, Sharma A, Maniataki E, Mourelatos Z. The microRNA world: small is mighty. Trends Biochem Sci 2003; 28: 534-40.
185. Adams BD, Claffey KP, White BA. Argonaute-2 expression is regulated by epidermal growth factor receptor and mitogenactivated protein kinase signaling and correlates with a transformed phenotype in breast cancer cells. Endocrinology 2009; 150: 14-23.
186. Li L, Yu C, Gao H, Li Y. Argonaute proteins: potential biomarkers for human colon cancer. BMC Cancer 2010; 10: 38.
187. Zhou Y, Chen L, Barlogie B, et al. High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2. Proc Natl Acad Sci USA 2010; 107: 7904-9.
188. Kim MS, Oh JE, Kim YR, et al. Somatic mutations and losses of expression of microRNA regulation-related genes AGO2 and TNRC6A in gastric and colorectal cancers. J Pathol 2010; 221: 139-46.
189. Yoo NJ, Hur SY, Kim MS, Lee JY, Lee SH. Immunohistochemical analysis of RNA-induced silencing complex-related proteins AGO2 and TNRC6A in prostate and esophageal cancers. APMIS 2010; 118: 271-6.
190. Zhao Y, Ransom JF, Li A, et al. Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2. Cell 2007;129: 303-17.
191. Chen JF, Murchison EP, Tang R, et al. Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure. Proc Natl Acad Sci 2008;105: 2111-6.
192. da Costa Martins PA, Bourajjaj M, Gladka M, et al. Conditional dicer gene deletion in the postnatal myocardium provokes spontaneous cardiac remodeling. Circulation 2008;118: 1567-76.
193. Watashi K, Yeung ML, Starost MF, Hosmane RS, Jeang KT. Identification of small molecules that suppress microRNA function and reverse tumorigenesis. J Biol Chem 2010; 285: 24707-16.
194. Melo S, Villanueva A, Moutinho C, et al. 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 2011; 108: 4394-9.
195. Shan G, Li Y, Zhang J, et al. A small molecule enhances RNA interference and promotes microRNA processing. Nat Biotechnol 2008; 26: 933-40.
196. Ovcharenko D, Kelnar K, Johnson C, Leng N, Brown D. Genomescale microRNA and small interfering RNA screens identify small RNA modulators of TRAILinduced apoptosis pathway. Cancer Res 2007; 67: 10782-10788.
197. Gironella M, Seux M, Xie MJ, et al. Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci USA 2007; 104: 1616-617.
198. Ota A, Tagawa H, Karnan S, et al. Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res 2004; 64: 3087-3095.
199. Hayashita Y, Osada H, Tatematsu Y, et al. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 2005; 65: 9628-632.
200. Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and downregulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2002; 99: 15524-5529.
201. Iorio MV, Ferracin M, Liu CG, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005; 65: 7065-7070.
202. Michael MZ, O'Connor SM, van Holst Pellekaan NG, Young GP, James RJ. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 2003; 1: 882-891.
203. Pekarsky Y, Santanam U, Cimmino A, et al. Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181. Cancer Res 2006; 66: 11590-3.
204. Debernardi S, Skoulakis S, Molloy G, Chaplin T, Dixon-McIver A, Young BD. MicroRNA miR-181a correlates with morphological sub-class of acute myeloid leukaemia and the expression of its target genes in global genome-wide analysis. Leukemia 2007; 21: 912-6.
205. Gravgaard KH, Lyng MB, Laenkholm AV, et al. The miRNA-200 family and miRNA-9 exhibit differential expression in primary versus corresponding metastatic tissue in breast cancer. Breast Cancer Res Treat 2012, Feb 1.
206. Valastyan S, Reinhardt F, Benaich N, et al. A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell 2009; 137: 1032-46.
207. Huang Q, Gumireddy K, Schrier M, et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol 2008; 10: 292-210.
208. Meister J, Schmidt MH. miR-126 and miR-126*: new players in cancer. Scientific World Journal 2010; 10: 2090-100.
209. Tavazoie SF, Alarcon C, Oskarsson T, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature 2008; 451: 147-152.
210. Sohn SY, Bae WJ, Kim JJ, Yeom KH, Kim VN, Cho Y. Crystal structure of human DGCR8 core. Nat Struct Mol Biol 2007; 14: 847-53.
211. Yeom KH, Lee Y, Han J, Suh MR, Kim VN. Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing. Nucleic Acids Res 2006; 34: 4622-9.
212. Senturia R, Faller M, Yin S, et al. Structure of the dimerization domain of DiGeorge critical region 8. Protein Sci 2010; 19: 1354-65.
213. Mueller GA, Miller MT, Derose EF, Ghosh M, London RE, Hall TM. Solution structure of the Drosha double-stranded RNAbinding domain. Silence 2010; 1: 2.
214. Okada C, Yamashita E, Lee SJ, et al. A high-resolution structure of the pre-microRNA nuclear export machinery. Science 2009; 326: 1275-9.
215. Takeshita D, Zenno S, Lee WC, Nagata K, Saigo K, Tanokura M. Homodimeric structure and double-stranded RNA cleavage activity of the C-terminal RNase III domain of human dicer. J Mol Biol 2007; 374: 106-20.
216. Du Z, Lee JK, Tjhen R, Stroud RM, James TL. Structural and biochemical insights into the dicing mechanism of mouse Dicer: a conserved lysine is critical for dsRNA cleavage. Proc Natl Acad Sci U S A 2008; 105: 2391-6.
217. Barraud P, Emmerth S, Shimada Y, Hotz HR, Allain FH, Bühler M. An extended dsRBD with a novel zinc-binding motif mediates nuclear retention of fission yeast Dicer. EMBO J 2011; 30: 4223-35.
218. Bouasker S, Simard MJ. Structural biology: Tracing Argonaute binding. Nature 2009; 461: 743-4.
219. Parker JS. How to slice: snapshots of Argonaute in action. Silence 2010; 1: 3.
220. Djuranovic S, Nahvi A, Green R. A parsimonious model for gene regulation by miRNAs. Science 2011; 331: 550-3.
221. Yan KS, Yan S, Farooq A, Han A, Zeng L, Zhou MM. Structure and conserved RNA binding of the PAZ domain. Nature 2003; 426: 468-74.
222. Song JJ, Liu J, Tolia NH, et al. The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding motif in RNAi effector complexes. Nat Struct Biol 2003; 10: 1026-32.
223. Lingel A, Simon B, Izaurralde E, Sattler M. Structure and nucleicacid binding of the Drosophila Argonaute 2 PAZ domain. Nature 2003; 426: 465-9.
224. Lingel A, Simon B, Izaurralde E, Sattler M. Nucleic acid 3'-end recognition by the Argonaute2 PAZ domain. Nat Struct Mol Biol 2004; 11: 576-7.
225. Ma JB, Ye K, Patel DJ. Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain. Nature 2004; 429: 318-22.
226. Song JJ, Smith SK, Hannon GJ, Joshua-Tor L. Crystal structure of Argonaute and its implications for RISC slicer activity. Science 2004; 305: 1434-7.
227. Sontheimer EJ, Carthew RW. Molecular biology. Argonaute journeys into the heart of RISC. Science 2004; 305: 1409-10.
228. Rivas FV, Tolia NH, Song JJ, et al. Purified Argonaute2 and an siRNA form recombinant human RISC. Nat Struct Mol Biol 2005; 12: 340-9.
229. Yuan YR, Pei Y, Ma JB, et al. Crystal structure of A. aeolicus argonaute, a site-specific DNA-guided endoribonuclease, provides insights into RISC-mediated mRNA cleavage. Mol Cell 2005; 19: 405-19.
230. Yuan YR, Pei Y, Chen HY, Tuschl T, Patel DJ. A potential protein-RNA recognition event along the RISC-loading pathway from the structure of A. aeolicus Argonaute with externally bound siRNA. Structure 2006; 14: 1557-65.
231. Rashid UJ, Paterok D, Koglin A, Gohlke H, Piehler J, Chen JC. Structure of Aquifex aeolicus argonaute highlights conformational flexibility of the PAZ domain as a potential regulator of RNAinduced silencing complex function. J Biol Chem 2007; 282: 13824-32.
232. Parker JS, Roe SM, Barford D. Structural insights into mRNA recognition from a PIWI domain-siRNA guide complex. Nature 2005; 434: 663-6.
233. Wang Y, Sheng G, Juranek S, Tuschl T, Patel DJ. Structure of the guide-strand-containing argonaute silencing complex. Nature 2008; 456: 209-13.
234. Wang Y, Juranek S, Li H, Sheng G, Tuschl T, Patel DJ. Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex. Nature 2008; 456: 921-6.
235. Wang Y, Juranek S, Li H, et al. Nucleation, propagation and cleavage of target RNAs in Ago silencing complexes. Nature 2009; 461: 754-61.
236. Frank F, Sonenberg N, Nagar B. Structural basis for 5'-nucleotide base-specific recognition of guide RNA by human AGO2. Nature 2010; 465: 818-22.
237. Frank F, Fabian MR, Stepinski J, et al. Structural analysis of 5'-mRNA-cap interactions with the human AGO2 MID domain. EMBO Rep 2011; 12: 415-20.
238. Boland A, Tritschler F, Heimstädt S, Izaurralde E, Weichenrieder O. Crystal structure and ligand binding of the MID domain of a eukaryotic Argonaute protein. EMBO Rep 2010; 11: 522-7.
239. Boland A, Huntzinger E, Schmidt S, Izaurralde E, Weichenrieder O. Crystal structure of the MID-PIWI lobe of a eukaryotic Argonaute protein. Proc Natl Acad Sci U S A 2011; 108: 10466-71.
240. Tian Y, Simanshu DK, Ma JB, Patel DJ. Structural basis for piRNA 2'-O-methylated 3'-end recognition by Piwi PAZ (Piwi/Argonaute/Zwille) domains. Proc Natl Acad Sci USA. 2011; 108: 903-10.
241. Schirle NT, MacRae IJ. The Crystal Structure of Human Argonaute2. Science. 2012 Apr 26;(April):1-4.
242. Elkayam E, Kuhn C-D, Tocilj A, Haase A, Greene E, Hannon G, et al. The Structure of Human Argonaute-2 in Complex with miR-20a. Cell. 2012 Jun 7;
243. Tan GS, Chiu CH, Garchow BG, Metzler D, Diamond SL, Kiriakidou M. Small Molecule Inhibition of RISC Loading. ACS Chem Biol 2012 Feb; 7: 403-10.
244. Yang SW, Chen HY, Yang J, Machida S, Chua NH, Yuan YA. Structure of Arabidopsis HYPONASTIC LEAVES1 and its molecular implications for miRNA processing. Structure 2010; 18: 594-605.