The emerging important role of microRNAs in the pathogenesis, diagnosis and treatment of human cancers

Pathology

Volumn 43, Issue 6, 2011, Pages 657-671

  Wilmott, James S ^a,b   Zhang, Xu Dong ^d   Hersey, Peter ^d   Scolyer, Richard A ^a,b,c  

^a ROYAL PRINCE ALFRED HOSPITAL   (Australia)

^b Department of Disciplines of Pathology ^*  (Australia)

^c UNIVERSITY OF SYDNEY   (Australia)

^d CALVARY MATER NEWCASTLE HOSPITAL   (Australia)

Author keywords

Cancer; Diagnosis; Melanoma; Microrna; Pathology; Prognosis; Therapy; Treatment

Indexed keywords

EID: 83055163828     PISSN: 00313025     EISSN: 14653931     Source Type: Journal    
DOI: 10.1097/PAT.0b013e32834a7358     Document Type: Article

References (252)

1. Michor F, Iwasa Y, Nowak MA. Dynamics of cancer progression. Nat Rev Cancer 2004; 4: 197-205. (Pubitemid 38337499)
2. Griffiths-Jones S,Saini HK, van Dongen S,Enright AJ.miRBase: toolsfor micro RNA genomics. Nucleic Acids Res 2008:D154-158. (Pubitemid 351149713)
3. Brennecke J, Stark A, Russell RB, Cohen SM. Principles of micro RNA-target recognition. PLoS Biol 2005; 3: e85.
4. Heale BSE, Keegan LP, McGurk L, et al. Editing independent effects of ADARs on the miRNA/si RNA pathways. EMBO J 2009; 28: 3145-56.
5. Bohnsack MT, Czaplinski K, Gorlich D. Exportin 5 is a Ran GTP-dependent ds RNA-binding protein that mediates nuclear export of pre-miRNAs. RNA 2004; 10: 185-91. (Pubitemid 38129823)
6. Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-micro RNAs and short hairpin RNAs. Genes Dev 2003; 17: 3011-6. (Pubitemid 38040764)
7. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: micro RNA biogenesis pathways and their regulation. Nat Cell Biol 2009; 11: 228-34.
8. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by micro RNAs: are the answers in sight? Nat Rev Genet 2008; 9: 102-14.
9. Jing Q, Huang S, Guth S, et al. Involvement of Micro RNA in AU-rich element-mediated m RNA instability. Cell 2005; 120: 623-34. (Pubitemid 40343075)
10. Valencia-Sanchez MA, Liu JD, Hannon GJ, Parker R. Control of transla-tion and m RNA degradation by miRNAs and si RNAs. Genes Dev 2006; 20: 515-24. (Pubitemid 43345317)
11. Liu JD, Valencia-Sanchez MA, Hannon GJ, Parker R. Micro RNA-depen-dent localization of targeted m RNAs to mammalian P-bodies. Nat Cell Biol 2005; 7: 719-23. (Pubitemid 40975754)
12. Sen GL, Blau HM. Argonaute 2/RISC resides in sites of mammalian m RNA decay known as cytoplasmic bodies. Nat Cell Biol 2005; 7: 633-6. (Pubitemid 40796987)
13. Liu X, Fortin K, Mourelatos Z. Micro RNAs: Biogenesis and molecular functions. Brain Pathol 2008; 18: 113-21.
14. Hutvagner G, Zamore PD. A micro RNA in a multiple-turnover RNAi enzyme complex. Science 2002; 297: 2056-60.
15. Calin GA, Sevignani C, Dan Dumitru C, et al. Human micro RNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 2004; 101: 2999-3004. (Pubitemid 38327724)
16. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F. A micro RNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 2006; 103: 2257-61. (Pubitemid 43271657)
17. Saito Y, Liang G, Egger G, et al. Specific activation of micro RNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modify-ing drugs in human cancer cells. Cancer Cell 2006; 9: 435-43. (Pubitemid 43832188)
18. Bandres E, Agirre X, Bitarte N, et al. Epigenetic regulation of micro RNA expression in colorectal cancer. Int J Cancer 2009; 125: 2737-43.
19. Lujambio A, Calin GA, Villanueva A, et al. A micro RNA DNA methyla-tion signature for human cancer metastasis. Proc Natl Acad Sci USA 2008; 105: 13556-61.
20. Wu XM,Xiao HS.miRNA smodulate the drug response of tumor cells. Sci China C Life Sci 2009; 52: 797-801.
21. Calin GA, Dumitru CD, Shimizu M, 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: 15524-9. (Pubitemid 35403967)
22. Tagawa H, Seto M. A micro RNA cluster as a target of genomic amplifica-tion in malignant lymphoma. Leukemia 2005; 19: 2013-6. (Pubitemid 41554018)
23. Hayashita Y, Osada H, Tatematsu Y, et al. A polycistronic micro RNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 2005; 65: 9628-32. (Pubitemid 41541436)
24. Bray I, Bryan K, Prenter S, et al. Widespread dysregulation of miRNAs by MYCN amplification and chromosomal imbalances in neuroblasto-ma: association of miRNA expression with survival. PLoS One 2009; 4: e7850.
25. Johannes HS, Sebastian H, Tobias O, et al. MYCN regulates oncogenic Micro RNAs in neuroblastoma. Int J Cancer 2008; 122: 699-704.
26. Chang TC, Yu DN, Lee YS, et al. Widespread micro RNA repression by Myc contributes to tumorigenesis. Nat Genet 2008; 40: 43-50.
27. Woods K, Thomson JM, Hammond SM. Direct regulation of an oncogenic micro-RNA cluster by E2F transcription factors. J Biol Chem 2007; 282: 2130-4. (Pubitemid 47076737)
28. Sylvestre Y, De Guire V, Querido E, et al. An E2F/miR-20a Autoregu-latory Feedback Loop. J Biol Chem 2007; 282: 2135-43.
29. Bommer GT, Gerin I, Feng Y, et al. p53-mediated activation of miRNA34 candidatetumor-suppressorgenes. Curr Biol2007; 17: 1298-307.
30. He L, He XY, Lim LP, et al. A micro RNA component of the p53 tumour suppressor network. Nature 2007; 447: 1130-4. (Pubitemid 47014436)
31. 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.
32. Muralidhar B, Goldstein L, Ng G, et al. Global micro RNA profiles in cervical squamous cell carcinoma depend on Drosha expression levels. J Pathol 2007; 212: 368-77. (Pubitemid 47099013)
33. Yoko K, Hisaaki T, Hirotaka O, et al. Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci 2005; 96: 111-5.
34. 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. (Pubitemid 40425386)
35. Buck AH, Perot J, Chisholm MA, et al. Post-transcriptional regulation of miR-27 in murine cytomegalovirus infection. RNA 2010; 16: 307-15.
36. Triboulet R, Mari B, Lin YL, et al. Suppression of micro RNA-silencing pathway by HIV-1 during virus replication. Science 2007; 315: 1579-82. (Pubitemid 46449475)
37. Liu C-G, Calin GA, Meloon B, et al. An oligonucleotide microchip for genome-wide micro RNA profiling in human and mouse tissues. Proc Natl Acad Sci USA 2004; 101: 9740-4. (Pubitemid 38869306)
38. Lu J, Getz G, Miska EA, et al. Micro RNA expression profiles classify human cancers. Nature 2005; 435: 834-8. (Pubitemid 40839735)
39. Stark MS, Tyagi S, Nancarrow DJ, et al. Characterization of the melanoma miRNAome by deep sequencing. PLoS One 2010; 5: 9.
40. Git A, Dvinge H, Salmon-Divon M, et al. Systematic comparison of microarray profiling, real-time PCR, and next-generation sequencing technologies for measuring differential micro RNA expression. RNA 2010; 16: 991-1006.
41. Li JH, Smyth P,Flavin R, et al. ComparisonofmiRNAexpressionpatterns using total RNA extracted from matched samples of formalin-fixed paraffin-embedded (FFPE) cells and snap frozen cells. BMC Biotechnol 2007; 7: 6.
42. Ach RA, Wang H, Curry B. Measuring micro RNAs: Comparisons of microarray and quantitative PCR measurements, and of different total RNA prep methods. BMC Biotechnol 2008; 8: 16.
43. Satzger I, Anika M, Uta K, et al. Micro RNA-15b represents an indepen-dent prognostic parameter and is correlated with tumor cell proliferation and apoptosis in malignant melanoma. Int J Cancer 2010; 126: 2553-62.
44. Pavlidis N, Briasoulis E, Hainsworth J, Greco FA. Diagnostic and therapeutic management of cancer of an unknown primary. Eur J Cancer 2003; 39: 1990-2005. (Pubitemid 37297755)
45. Bryant A, Lutherborrow M, Ma D. The clinicopathological relevance of micro RNA in normal and malignant haematopoiesis. Pathology 2009; 41: 204-13.
46. Takamizawa J, Konishi H, Yanagisawa K, et al. Reduced expression of the let-7 micro RNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 2004; 64: 3753-6. (Pubitemid 38697282)
47. Yanaihara N, Caplen N, Bowman E, et al. Unique micro RNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 2006; 9: 189-98. (Pubitemid 43357945)
48. Shell S, Park SM, Radiabi AR, et al. Let-7 expression defines two differentiation stages of cancer. Proc Natl Acad Sci USA 2007; 104: 11400-5. (Pubitemid 47175152)
49. Childs G, Fazzari M, Kung G, et al. Low-level expression ofmicro RNAs let-7d and miR-205 are prognostic markers of head and neck squamous cell carcinoma. Am J Pathol 2009; 174: 736-45.
50. Johnson SM, Grosshans H, Shingara J, et al. RAS is regulated by the let-7 micro RNA family. Cell 2005; 120: 635-47. (Pubitemid 40343076)
51. Christensen BC, Moyer BJ, Avissar M, et al. A let-7 micro RNA-binding site polymorphism in the KRAS 3' UTR is associated with reduced survival in oral cancers. Carcinogenesis 2009; 30: 1003-7.
52. Dong QC, Meng P, Wang T, et al. Micro RNA Let-7a inhibits proliferation of human prostate cancer cells in vitro and in vivo by targeting E2F2 and CCND2. PLoS One 2010; 5: 7.
53. Yan LX, Huang XF, Shao Q, 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.
54. Caramuta S, Egyhazi S, Rodolfo M, et al. Micro RNA expression profiles associated with mutational status and survival in malignant melanoma. J Invest Dermatol 2010; 130: 2062-70.
55. Fulci V, Chiaretti S, Goldoni M, et al. Quantitative technologies establish a novel micro RNA profile of chronic lymphocytic leukemia. Blood 2007; 109: 4944-51. (Pubitemid 46827793)
56. Xia L, Zhang DX, Du R, et al. miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer 2008; 123: 372-9. (Pubitemid 351842022)
57. Cimmino A, Calin GA, Fabbri M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 2005; 102: 13944-9. (Pubitemid 41377683)
58. Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 2007; 26: 1324-37. (Pubitemid 46328466)
59. Liu Q, Fu H, Sun F, et al. miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes. Nucleic Acids Res 2008; 36: 5391-404.
60. Karaa Zn S, Iacovoni JS, Bastide A, Lacazette E, Touriol C, Prats H. The VEGF IRESes are differentially susceptible to translation inhibition by miR-16. RNA 2009; 15: 249-54.
61. Bottoni A, Piccin D, Tagliati F, Luchin A, Zatelli MC, Degli Uberti EC miR-15a and miR-16-1 down-regulation in pituitary adenomas. J Cell Physiol 2005; 204: 280-5. (Pubitemid 40776831)
62. Dixon-McIver A, East P, Mein CA, et al. Distinctive patterns of micro-RNA expression associated with karyotype in acute myeloid leukaemia. PLoS One 2008; 3: e2141.
63. Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TL, Visakorpi T. Micro RNA expression profiling in prostate cancer. Cancer Res 2007; 67: 6130-5. (Pubitemid 47037493)
64. Bandi N, Zbinden S, Gugger M, et al.miR-15aandmiR-16areimplicated in cell cycle regulation in a Rb-dependent manner and are frequently deleted or down-regulated in non-small cell lung cancer. Cancer Res 2009; 69: 5553-9.
65. He L, Thomson JM, Hemann MT, et al. A micro RNA polycistron as a potential human oncogene. Nature 2005; 435: 828-33. (Pubitemid 40839734)
66. Dews M, Homayouni A, Yu D, et al. Augmentation oftumor angiogenesis by a Myc-activated micro RNA cluster. Nat Genet 2006; 38: 1060-5. (Pubitemid 44325933)
67. Mendell JT. miRiad Roles for the miR-17-92 Cluster in Development and Disease. Cell 2008; 133: 217-22. (Pubitemid 351508308)
68. Xiao CC, Srinivasan L, Calado DP, et al. Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lympho-cytes. Nat Immunol 2008; 9: 405-14. (Pubitemid 351405110)
69. Inomata M, Tagawa H, Guo YM, Kameoka Y, Takahashi N, Sawada K. Micro RNA-17-92 down-regulates expression of distinct targets in differ-ent B-cell lymphoma subtypes. Blood 2009; 113: 396-402.
70. Wong P, Iwasaki M, Somervaille TC, et al. The miR-17-92 micro RNA polycistron regulates MLL leukemia stem cell potential by modulating p21 expression. Cancer Res 2010; 70: 3833-42.
71. Zhang L, Huang J, Yang N, et al. micro RNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci USA 2006; 103: 9136-41. (Pubitemid 43902545)
72. Hossain A, Kuo MT, Saunders GF. Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 m RNA. Mol Cell Biol 2006; 26: 8191-201. (Pubitemid 44631015)
73. Yu Z, Wang C, Wang M, et al. A cyclin D1/micro RNA 17/20 regulatory feedback loop in control of breast cancer cell proliferation. J Cell Biol 2008; 182: 509-17.
74. Chan JA, Krichevsky AM, Kosik KS. Micro RNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 2005; 65: 6029-33. (Pubitemid 40994386)
75. Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY. miR-21-mediated tumor growth. Oncogene 2006; 26: 2799-803. (Pubitemid 46663837)
76. Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T Micro RNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 2007; 133: 647-58. (Pubitemid 47187346)
77. Loffler D, Brocke-Heidrich K, Pfeifer G, et al. Interleukin-6 dependent survival ofmultiple myeloma cells involves the Stat3-mediated induction of micro RNA-21 through a highly conserved enhancer. Blood 2007; 110: 1330-3. (Pubitemid 47281433)
78. Talotta F, Cimmino A, Matarazzo MR, Casalino L, De Vita G, D'Esposito M. An autoregulatory loop mediated by miR-21 and PDCD4 controls the AP-1 activity in RAS transformation. Oncogene 2009; 28: 73-84.
79. Davis BN, Hilyard AC, Lagna G, Hata A. SMAD proteins control DROSHA-mediated micro RNA maturation. Nature 2008; 454: 56-61. (Pubitemid 351931982)
80. Schetter AJ, Leung SY, Sohn JJ, et al. Micro RNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarci-noma. JAMA 2008; 299: 425-36. (Pubitemid 351185951)
81. Markou A, Tsaroucha EG, Kaklamanis L, Fotinou M, Georgoulias V, Lianidou ES. Prognostic value of mature micro RNA-21 and micro RNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR. Clin Chem 2008; 54: 1696-704.
82. Hwang JH, Voortman J, Giovannetti E, et al. Identification ofmicro RNA-21 as a biomarker for chemoresistance and clinical outcome following adjuvant therapy in resectable pancreatic cancer. PLoS One 2010; 5: 12.
83. Eis PS, Tam W, Sun L, et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci USA 2005; 102: 3627-32. (Pubitemid 40354662)
84. Kong W, He LL, Coppola M, et al. Micro RNA-155 regulates cell survival, growth, and chemosensitivity by targeting FOXO3a in breast cancer. J Biol Chem 2010; 285: 17869-7.
85. Kong W, Yang H, He L, et al. Micro RNA-155 is regulated by the transforming growth factor {beta}/smad pathway and contributes to epithelial cell plasticity by targeting Rho A. Mol Cell Biol 2008; 28: 6773-84.
86. Jiang S, Zhang H-W, Lu M-H, et al. Micro RNA-155 functions as an oncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Cancer Res 2010; 70: 3119-27.
87. 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: 16170-5. (Pubitemid 350099380)
88. O'Connell RM, Chaudhuri AA, Rao DS, Baltimore D. Inositol phospha-tase SHIP1 is a primary target ofmiR-155. Proc Natl Acad Sci USA 2009; 106: 7113-8.
89. Rai D, Kim S-W, McKeller MR, Dahia PLM, Aguiar RCT. Targeting of SMAD5 links micro RNA-155 to the TGF-I pathway and lymphomagen-esis. Proc Natl Acad Sci USA 2009; 107: 3111-6.
90. Greither T, Grochola LF, Udelnow A, Lautenschlager C, Wurl P, Taubert H. Elevated expression of micro RNAs 155, 203, 210 and 222 in pancreatic tumors is associated with poorer survival. Int J Cancer 2009; 126: 73-80.
91. Raponi M, Dossey L, Jatkoe T, et al. Micro RNA classifiers for predicting prognosis of squamous cell lung cancer. Cancer Res 2009; 69: 5776-83.
92. Meister G, Landthaler M, Dorsett Y, Tuschl T. Sequence-specific inhibi-tion of micro RNA- and si RNA-induced RNA silencing. RNA 2004; 10: 544-50. (Pubitemid 38241013)
93. Stenvang J, Silahtaroglu AN, Lindow M, Elmen J, Kauppinen S. The utility of LNA in micro RNA-based cancer diagnostics and therapeutics. Semin Cancer Biol 2008; 18: 89-102.
94. Krutzfeldt J, Kuwajima S, Braich R, et al. Specificity, duplex degradation and subcellular localization of antagomirs. Nucleic Acids Res 2007; 35: 2885-92. (Pubitemid 47073627)
95. Felicetti F, Errico MC, Bottero L, et al. The promyelocytic leukemia zinc finger-micro RNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms. Cancer Res 2008; 68: 2745-54. (Pubitemid 351556272)
96. Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by micro RNA 10b in breast cancer. Nature 2007; 449: 682-8. (Pubitemid 47552092)
97. Ma L, Reinhardt F, Pan E, et al. Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nature Biotechnol 2010; 28: U341-67.
98. Wolfrum C, Shi S, Jayaprakash KN, et al. Mechanisms and optimization of in vivo delivery of lipophilic si RNAs. Nature Biotechnol 2007; 25: 1149-57. (Pubitemid 47538115)
99. Bijsterbosch MK, Rump ET, Vrueh RLAD, et al. Modulation of plasma protein binding and in vivo liver cell uptake of phosphorothioate oligo- deoxynucleotides by cholesterol conjugation. Nucleic Acids Res 2000; 28: 2717-25. (Pubitemid 30598756)
100. Krutzfeldt J, Rajewsky N, Braich R, et al. Silencing of micro RNAs in vivo with 'antagomirs'. Nature 2005; 438: 685-9. (Pubitemid 41740580)
101. Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, Kauppinen S, Orum H. Therapeutic Silencing of micro RNA-122 in primates with chronic hepatitis C virus infection. Science 2001; 327: 198-201.
102. Ebert MS, Neilson JR, Sharp PA. Micro RNA sponges. competitive inhibitors of small RNAs in mammalian cells. Nat Methods 2007; 4: 721-6. (Pubitemid 47338166)
103. Valastyan S, Reinhardt F, Benaich N, et al. A pleiotropically acting micro RNA, miR-31, inhibits breast cancer metastasis. Cell 2009; 137: 1032-46.
104. Ma L, Young J, Prabhala H, et al. miR-9, a MYC/MYCN-activated micro RNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol 2010; 12: U247-52.
105. Xiao JN, Yang BF, Lin HX, Lu YJ, Luo XB, Wang ZG. Novel approaches for gene-specific interference manipulating actions of via micro RNAS. Examination on the pacemaker channel genes HCN2 and HCN4. J Cell Physiol 2007; 212: 285-92.
106. Silber J, Lim DA, Petritsch C, et al. miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells. BMC Medicine 2008; 6: 17.
107. Luthra R, Singh RR, Luthra MG, et al. Micro RNA-196a targets annexin A1: a micro RNA-mediated mechanism of annexin A1 downregulation in cancers. Oncogene 2008; 27: 6667-78.
108. Ji Q, Hao XB, Meng Y, et al. Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres. BMC Cancer 2008; 8: 12.
109. Trang P, Medina PP, Wiggins JF. Regression ofmurine lung tumors by the let-7 micro RNA. Oncogene 2010; 29: 1580-7.
110. Wiggins JF, Ruffino L, Kelnar K, et al. Development of a lung cancer therapeutic based on the tumor suppressor micro RNA-34. Cancer Res 2010; 70: 5923-30.
111. Kota J, Chivukula RR, O'Donnell KA, et al. Therapeutic micro RNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 2009; 137: 1005-17.
112. Yi R, Fuchs E. Micro RNA-mediated control in the skin. Cell Death Differ 2010; 17: 229-35.
113. Hutvagner G, Simard MJ, Mello CC, Zamore PD. Sequence-specific inhibition of small RNA function. PLoS Biol 2004; 2: 465-75.
114. Grimm D, Streetz KL, Jopling CL, et al. Fatality in mice due to over-saturation of cellular micro RNA/short hairpin RNA pathways. Nature 2006; 441: 537-41. (Pubitemid 44050158)
115. McBride JL, Boudreau RL, Harper SQ, et al. Artificial miRNAs mitigate sh RNA-mediated toxicity in the brain: Implications for the therapeutic development of RNAi. Proc Natl Acad Sci USA 2008; 105: 5868-73. (Pubitemid 351758464)
116. Donsante A, Miller DG, Li Y, et al. AAV vector integration sites in mouse hepatocellular carcinoma. Science 2007; 317: 477. (Pubitemid 47196106)
117. Zhang JJ, Huang SL,Zhang H,et al. Targetedknockdown of Bcl2intumor cells using a synthetic TRAIL 3'-UTRmicro RNA. Int J Cancer2010; 126: 2229-39.
118. Esteller M. Cancer epigenomics: DNA methylomes and histone-modifi-cation maps. Nat Rev Genet 2007; 8: 286-98. (Pubitemid 46439286)
119. Miller TE, Ghoshal K, Ramaswamy B, et al. Micro RNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. JBiol Chem 2008; 283: 29897-903.
120. Sorrentino A, Liu CG, Addario A, Peschle C, Scambia G, Ferlini C. Role of micro RNAs in drug-resistant ovarian cancer cells. Gynecol Oncol 2008; 111: 478-86.
121. Blower PE, Chung JH, Verducci JS, et al. Micro RNAs modulate the chemosensitivity of tumor cells. Mol Cancer Ther 2008; 7: 1-9.
122. Meng FY, Henson R, Lang M, et al. Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology 2006; 130: 2113-29. (Pubitemid 43816961)
123. Wan PTC, Garnett MJ, Roe SM, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 2004; 116: 855-67. (Pubitemid 38410730)
124. Kimura ET, Nikiforova MN, Zhu ZW, Knauf JA, Nikiforov YE, Fagin JA. High prevalence of BRAF mutations in thyroid cancer: Genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res 2003; 63: 1454-7. (Pubitemid 36373628)
125. Satyamoorthy K, Li G, Gerrero MR, et al. Constitutive mitogen-activated protein kinase activation in melanoma is mediated by both BRAF muta-tions and autocrine growth factor stimulation. Cancer Res 2003; 63: 756-9. (Pubitemid 36231971)
126. Deng GR, Bell I, Crawley S, et al. BRAF mutation is frequently present in sporadic colorectal cancer with methylated h MLH1, but not in hereditary nonpolyposis colorectal cancer. Clin Cancer Res 2004; 10: 191-5. (Pubitemid 38114179)
127. Gemignani ML, Schlaerth AC, Bogomolniy F, et al. Role of KRAS and BRAF gene mutations in mucinous ovarian carcinoma. Gynecol Oncol 2003; 90: 378-81. (Pubitemid 36952030)
128. Nikiforova MN, Tseng GC, Steward D, Diorio D, Nikiforov YE. Micro-RNA expression profiling of thyroid tumors: Biological significance and diagnostic utility. J Clin Endocrinol Metab 2008; 93: 1600-8. (Pubitemid 351656494)
129. Sheu SY, Grabellus F, Schwertheim S, Handke S, Worm K, Schmid KW. Lack of correlation between BRAF V600E mutational status and the expression profile of a distinct set of miRNAs in papillary thyroid carcinoma. Horm Metab Res 2009; 41: 482-7.
130. Bandres E, Cubedo E, Agirre X, et al. Identification by Real-time PCR of 13 mature micro RNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer 2006; 5: 10.
131. Lowery AJ, Miller N, Devaney A, et al. Micro RNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res 2009; 11: 18.
132. Huang TH,Wu FT,Loeb GB, et al.Up-regulationofmiR-21 by HER2/neu signaling promotes cell invasion. J Biol Chem 2009; 284: 18515-24.
133. Muralidhar B, Goldstein LD, Ng G, et al. Global micro RNA profiles in cervical squamous cell carcinoma depend on Drosha expression levels. J Pathol 2007; 212: 368-77. (Pubitemid 47099013)
134. Chiosea S, Jelezcova E, Chandran U, et al. Up-regulation of dicer, a component of the micro RNA machinery, in prostate adenocarcinoma. Am J Pathol2006; 169: 1812-20. (Pubitemid 351182010)
135. Sempere LF, Christensen M, Silahtaroglu A, et al. Altered micro RNA expression confined to specific epithelial cell subpopulations in breast cancer. Cancer Res 2007; 67: 11612-20.
136. Yang H, Kong W, He L, et al. Micro RNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res 2008; 68: 425-33. (Pubitemid 351380068)
137. Nam EJ, Yoon HJ, Kim SW, et al. Micro RNA expression profiles in serous ovarian carcinoma. Clin Cancer Res 2008; 14: 2690-5.
138. Schultz J, Lorenz P, Gross G, Ibrahim S, Kunz M. Micro RNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth. Cell Res 2008; 18: 549-57. (Pubitemid 351630945)
139. Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TLJ, Visakorpi T. Micro RNA expression profiling in prostate cancer. Cancer Res 2007; 67: 6130-5. (Pubitemid 47037493)
140. Amaral FC, Torres N, Saggioro F, et al. Micro RNAs differentially expressed in ACTH-secreting pituitary tumors. J Clin Endocrinol Metab 2009; 94: 320-3.
141. Lee EJ, Gusev Y, Jiang JM, et al. Expression profiling identifies micro-RNA signature in pancreatic cancer. Int J Cancer 2007; 120: 1046-54. (Pubitemid 46214304)
142. Lee YS, Dutta A. The tumor suppressor micro RNA let-7 represses the HMGA2 oncogene. Genes Dev 2007; 21: 1025-30. (Pubitemid 46686471)
143. Sampson VB, Rong NH, Han J, et al. Micro RNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res 2007; 67: 9762-70. (Pubitemid 47621223)
144. Muller DW, Bosserhoff AK. Integrin beta 3 expression is regulated by let-7a miRNA in malignant melanoma. Oncogene 2008; 27: 6698-706.
145. Lehmann U, Hasemeier B, Christgen M, et al. Epigenetic inactivation of micro RNA gene hsa-mir-9-1 in human breast cancer. J Pathol 2008; 214: 17-24.
146. Hildebrandt MAT, Gu J, Lin J, et al. Hsa-miR-9 methylation status is associated with cancer development and metastatic recurrence in patients with clear cell renal cell carcinoma. Oncogene 2010; 29: 5724-8.
147. Malzkorn B, Wolter M, Liesenberg F, et al. Identification and functional characterization of micro RNAs involved in the malignant progression of gliomas. Brain Pathol 2009; 20: 539-50.
148. Calin GA, Ferracin M, Cimmino A, et al. A Micro RNA signature associated with prognosis and progression in chronic lymphocytic leu-kemia. N Engl J Med 2005; 353: 1793-801. (Pubitemid 41549891)
149. Baffa R, Fassan M, Volinia S, et al. Micro RNA expression profiling of human metastatic cancers identifies cancer gene targets. J Pathol 2009; 219: 214-21.
150. Hiroki E, Akahira J, Suzuki F, et al. Changes in micro RNA expression levels correlate with clinicopathological features and prognoses in en-dometrial serous adenocarcinomas. Cancer Sci 2009; 101: 241-9.
151. Ciafre SA, Galardi S, Mangiola A, et al. Extensive modulation of a set of micro RNAs in primary glioblastoma. Biochem Biophys Res Commun 2005; 334: 1351-8. (Pubitemid 41074723)
152. Zhang Y, Li M, Wang H, et al. Profiling of 95 micro RNAs in pancreatic cancer cell lines and surgical specimens by real-time PCR analysis. World J Surg 2009; 33: 698-709.
153. Chen J, Feilotter HE, Pare GC, et al. Micro RNA-193b represses cell proliferation and regulates cyclin D1in melanoma. Am J Pathol 2010; 176: 2520-9.
154. Wang L, Tang H, Thayanithy V, et al. Gene networks and micro RNAs implicated in aggressive prostate cancer. Cancer Res 2009; 69: 9490-7.
155. Kaddar T, Rouault J-P, Chien WW, et al. TwonewmiR-16targets: caprin-1 and HMGA1, proteins implicated in cell proliferation. Biol Cell 2009; 101: 511-24.
156. Kim Y-K, Yu J, Han TS, et al. Functional links between clustered micro RNAs: suppression of cell-cycle inhibitors by micro RNA clusters in gastric cancer. Nucleic Acids Res 2009; 37: 1672-81.
157. Diosdado B, van de Wiel M, Droste J, et al. miR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression. Br J Cancer 2009; 101: 707-14.
158. Li Y, Tan WQ, Neo TWL, et al. Role of the miR-106b-25 micro RNA cluster in hepatocellular carcinoma. Cancer Sci 2009; 100: 1234-42.
159. O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulatedmicro RNAsmodulate E2F1 expression.Nature2005;435: 839-43.
160. Ivanovska I, Ball AS, Diaz RL, et al. Micro RNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression. Mol Cell Biol 2008; 28: 2167-74. (Pubitemid 351429964)
161. van Haaften G, AgamiR. Tumorigenicity of the miR-17-92 cluster distilled. Genes Devel 2010; 24: 1-4.
162. Iorio MV, Ferracin M, Liu CG, et al. Micro RNA gene expression dereg-ulation in human breast cancer. Cancer Res 2005; 65: 7065-70. (Pubitemid 41161233)
163. Chang SS, Jiang WW, Smith I, et al. Micro RNA alterations in head and neck squamous cell carcinoma. Int J Cancer 2008; 123: 2791-7.
164. Mathe EA, Nguyen GH, Bowman ED, et al. Micro RNA expression in squamous
165. Zhang Z, Li Z, Gao C, et al. miR-21 plays a pivotal role in gastric cancer pathogenesis and progression. Lab Invest 2008; 88: 1358-66.
166. Dahiya N, Sherman-Baust CA,Wang TL, et al. Micro RNA expression and identification of putative miRNA targets in ovarian cancer. PLoS One 2008; 3: e2436.
167. Sheu SY, Grabellus F, Schwertheim S, Worm K, Broecker-Preuss M, Schmid KW. Differential miRNA expression profiles in variants of papillary thyroid carcinoma and encapsulated follicular thyroid tumours. Br J Cancer 2009; 102: 376-82.
168. Gabriely G, Wurdinger T, Kesari S, et al. Micro RNA 21 promotes glioma invasion by targeting matrix met alloproteinase regulators. Mol Cell Biol 2008; 28: 5369-80.
169. Guo JM, Miao Y, Xiao BX, et al. Differential expression of micro RNA species in human gastric cancer versus non-tumorous tissues. J Gastro-enterol Hepatol 2009; 24: 652-7.
170. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH. Programmed cell death 4 (PDCD4) is an important functional target of the micro RNA miR-21 in breast cancer cells. J Biol Chem 2008; 283: 1026-33.
171. Qi L, Bart J, Tan L, et al. Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma. BMC Cancer 2009; 9: 163.
172. Chan JA, Krichevsky AM, Kosik KS. Micro RNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 2005; 65: 6029-33. (Pubitemid 40994386)
173. Pandey DP, Picard D. miR-22 inhibits estrogen signaling by directly targeting the estrogen receptor alpha m RNA. Mol Cell Biol 2009; 29: 3783-90.
174. Bar N, Dikstein R. miR-22 forms a regulatory loop in PTEN/AKT pathway and modulates signaling kinetics. PLoS One 2010; 5: e10859.
175. Xiong J, Du Q, Liang Z. Tumor-suppressive micro RNA-22 inhibits the transcription of E-box-containing c-Myc target genes by silencing c-Myc binding protein. Oncogene 2010; 29: 4980-8.
176. Huse JT, Brennan C, Hambardzumyan D, et al. The PTEN-regulating micro RNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo. Genes Devel 2009; 23: 1327-37.
177. Mott JL, Kobayashi S, Bronk SF, Gores GJ. mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene 2007; 26: 6133-40. (Pubitemid 47414372)
178. Slaby O, Svoboda M, Fabian P, et al. Altered expression ofmiR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology 2007; 72: 397-402. (Pubitemid 351238155)
179. Gallardo E, Navarro A, Vinolas N, et al. miR-34a as a prognostic marker of relapse in surgically resected non-small-cell lung cancer. Carcinogen-esis 2009; 30: 1903-9.
180. Migliore C, Petrelli A, Ghiso E, et al. Micro RNAs impair MET-mediated invasive growth. Cancer Res 2008; 68: 10128-36.
181. Yu S, Lu Z, Liu C, et al. miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer. Cancer Res 2010; 70: 6015-25.
182. Guttilla IK, White BA. Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells. J Biol Chem 2009; 284: 23204-16.
183. Strillacci A, Griffoni C, Sansone P, et al. miR-101 downregulation is involved in cyclooxygenase-2 overexpression in human colon cancer cells. Exp Cell Res 2009; 315: 1439-47.
184. Su H, Yang JR, Xu T. Micro RNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Res 2009; 69: 1135-42.
185. Varambally S, Cao Q, Mani RS, et al. Genomic loss of micro RNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science 2008; 322: 1695-9.
186. Gramantieri L, Ferracin M, Fornari F, et al. Cyclin g1 is a target of miR-122a, a Micro RNA frequently down-regulated in human hepatocellular carcinoma. Cancer Res 2007; 67: 6092-9. (Pubitemid 47037488)
187. Shi XB, Xue L, Yang J, et al. An androgen-regulated miRNA suppresses Bak1 expression and induces androgen-independent growth of prostate cancer cells. Proc Natl Acad Sci USA 2007; 104: 19983-8.
188. Murakami Y, Yasuda T, Saigo K, et al. Comprehensive analysis of micro RNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene 2006; 25: 2537-45.
189. Zhou M, Liu ZX, Zhao YH. Micro RNA-125b confers the resistance of breast cancer cells to paclitaxel through suppression ofpro-apoptotic Bcl-2 antagonist killer 1 (Bak1) expression. J Biol Chem 2010; 285: 21496-507.
190. Scott GK, Goga A, Bhaumik D, Berger CE, Sullivan CS, Benz CC. Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b. J Biol Chem 2007; 282: 1479-86. (Pubitemid 47076526)
191. Dacic S, Kelly L, Shuai Y,Nikiforova MN.miRNA expression profiling of lung adenocarcinomas: correlation with mutational status. Mod Pathol 2010; 23: 1577-82.
192. Balaguer F, Link A, Lozano JJ, et al. Epigenetic silencing ofmiR-137 is an early event in colorectal carcinogenesis. Cancer Res 2010; 70: 6609-18.
193. Bemis LT, Chen R, Amato CM, et al. Micro RNA-137 targets micro-phthalmia-associated transcription factor in melanoma cell lines. Cancer Res 2008; 68: 1362-8. (Pubitemid 351346843)
194. Wong CC,Wong CM,Tung EK, et al.The micro RNA miR-139 suppresses metastasis and progression of hepatocellular carcinoma by down-regulat-ing rho-kinase 2. Gastroenterology 2011; 140: 322-31.
195. Corbetta S, Vaira V, Guarnieri V, et al. Differential expression of micro-RNAs in human parathyroid carcinomas compared with normal parathyr-oid tissue. Endocr Relat Cancer 2010; 17: 135-46.
196. Hu MH, Xia M, Chen XB, et al. Micro RNA-141 regulates smad inter-acting protein 1 (SIP1) and inhibits migration and invasion of colorectal cancer cells. Dig Dis Sci 2010; 55: 2365-72.
197. Du Y, Xu Y, Ding L, et al. Down-regulation of miR-141 in gastric cancer and its involvement in cell growth. J Gastroenterol 2009; 44: 556-61.
198. Lee J-W, Park Y-A, Choi J-J, et al. The expression of the miRNA-200 family in endometrial endometrioid carcinoma. Gynecol Oncol 2011; 120: 56-62.
199. Jung M, Mollenkopf H-J, Grimm C, et al. Micro RNA profiling of clear cell renal cell cancer identifies a robust signature to define renal malig-nancy. J Cell Mol Med 2009; 13: 3918-28.
200. Kent OA, Chivukula RR, Mullendore M, et al. Repression of the miR-143/ 145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway. Genes Dev 2010; 24: 2754-9.
201. Akao Y, Nakagawa Y, Kitade Y, Kinoshita T, Naoe T. Downregulation of micro RNAs-143 and -145 in B-cell malignancies. Cancer Sci 2007; 98: 1914-20. (Pubitemid 350002197)
202. Wang Y, Lee CGL. Micro RNA and cancer - focus on apoptosis. J Cell Mol Med 2009; 13: 12-23.
203. He HL, Jazdzewski K, Li W, et al. The role of micro RNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA 2005; 102: 19075-80. (Pubitemid 43049568)
204. Hurst DR, Edmonds MD, Scott GK, Benz CC, Vaidya KS, Welch DR. Breast cancer metastasis suppressor 1 up-regulates miR-146, which suppresses breast cancer metastasis. Cancer Res 2009; 69: 1279-83.
205. Jazdzewski K, de la Chapelle A. Genomic sequence matters A SNP in micro RNA-146a can turn anti-apoptotic. Cell Cycle 2009; 8: 1642-3.
206. Liu H, Brannon A, Reddy A, et al. Identifying m RNA targets of micro-RNA dysregulated in cancer: with application to clear cell renal cell carcinoma. BMC Syst Biol 2010; 4: 51.
207. Katada T, Ishiguro H, Kuwabara Y, et al. micro RNA expression profile in undifferentiated gastric cancer. Int J Oncol 2009; 34: 537-42.
208. Schaefer A, Jung M, Mollenkopf HJ, et al. Diagnostic and prognostic implications of micro RNA profiling in prostate carcinoma. Int J Cancer 2010; 126: 1166-76.
209. Philippidou D, Schmitt M, Moser D, et al. Signatures of micro RNAs and selected micro RNA target genes in human melanoma. Cancer Res 2010; 70: 4163-73.
210. Debernardi S, Skoulakis S, Molloy G, Chaplin T, Dixon-McIver A, Young BD. Micro RNA 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. (Pubitemid 46672066)
211. Pallante P, Visone R, Ferracin M, et al. Micro RNA deregulation in human thyroid papillary carcinomas. Endocr Relat Cancer 2006; 13: 497-508. (Pubitemid 43886672)
212. 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. (Pubitemid 46094168)
213. Wang B, Hsu SH, Majumder S, et al. TGFbeta-mediated upregulation of hepatic miR-181b promotes hepatocarcinogenesis by targeting TIMP3. Oncogene 2009; 29: 1787-97.
214. Segura MF, Hanniford D, Menendez S, et al. Aberrant miR-182 expres-sion promotes melanoma metastasis by repressing FOXO3 and micro-phthalmia-associated transcription factor. Proc Natl Acad Sci USA 2009; 106: 1814-9.
215. Sun Y, Fang R, Li C, et al. Hsa-mir-182 suppresses lung tumorigenesis through down regulation of RGS17 expression in vitro. Biochem Biophys Res Commun 2010; 396: 501-7.
216. Sirotkin AV, Lauková M, Ovcharenko D, Brenaut P, Mlync?ek M. Identi-fication of Micro RNAs controlling human ovarian cell proliferation and apoptosis. J Cell Physiol 2010; 223: 49-56.
217. Motoyama K, Inoue H, Takatsuno Y, et al. Over- and under-expressed micro RNAs in human colorectal cancer. Int J Oncol 2009; 34: 1069-75.
218. Li JP, Fu HJ, Xu CW, et al. miR-183 inhibits TGF-beta 1-induced apoptosis by downregulation of PDCD4 expression in human hepatocel-lular carcinoma cells. BMC Cancer 2010; 10: 10.
219. Sarver AL, Li LH, Subramanian S. Micro RNA miR-183 functions as an oncogene by targeting the transcription factor EGR1 and promoting tumor cell migration. Cancer Res 2010; 70: 9570-80.
220. Lowery AJ, Miller N, Dwyer RM, Kerin MJ. Dysregulated miR-183 inhibits migration in breast cancer cells. BMC Cancer 2010; 10: 12.
221. Li GR, Luna C, Qiu JM, Epstein DL, Gonzalez P. Targeting of Integrin beta 1 and Kinesin 2 alpha by Micro RNA 183. J Biol Chem 2010; 285: 5461-71.
222. Song B, Wang Y, Kudo K, Gavin EJ, Xi YG, Ju JF. miR-192 Regulates Dihydrofolate Reductase and Cellular Proliferation through the p53-micro RNA Circuit. Clin Cancer Res 2008; 14: 8080-6.
223. Yang S, Du J, Wang ZQ, et al. Dual mechanism of delta EF1 expression regulated by bone morphogenetic protein-6 in breast cancer. Int J Biochem Cell Biol 2009; 41: 853-61.
224. Pichiorri F, Suh S-S, Rocci A, et al. Downregulation of p53-inducible micro RNAs 192, 194, and 215 impairs the p53/MDM2 autoregulatory loop in multiple myeloma development. Cancer Cell 2010; 18: 367-81.
225. Hino K, Tsuchiya K, Fukao T, et al. Inducible expression of micro RNA-194 is regulated by HNF-1 alpha during intestinal epithelial cell differ-entiation. RNA 2008; 14: 1433-42. (Pubitemid 351872199)
226. Xu T, Zhu Y, Xiong YJ, Ge YY, Yun JP, Zhuang SM. Micro RNA-195 suppresses tumorigenicity and regulates G(1)/S transition of human hepatocellular carcinoma cells. Hepatology 2009; 50: 113-21.
227. Liu L, Chen L, Xu YX, Li R, Du XH. micro RNA-195 promotes apoptosis and suppresses tumorigenicity of human colorectal cancer cells. Biochem Biophys Res Commun 2010; 400: 236-40.
228. Kim S, Lee UJ, Kim MN, et al. Micro RNA miR-199a* regulates the MET proto-oncogene and the downstream extracellular signal-regulated kinase 2 (ERK2)*. J Biol Chem 2008; 283: 18158-66.
229. Chen R,Alvero AB, Silasi DA, et al. Regulationof IKKbetaby miR-199a affects NF-kappa B activity in ovarian cancer cells. Oncogene 2008; 27: 4712-23.
230. Iorio MV, Visone R, Di Leva G, et al. Micro RNA signatures in human ovarian cancer. Cancer Res 2007; 67: 8699-707. (Pubitemid 47437445)
231. Gregory PA, Bert AG,Paterson EL, et al.Themir-200family andmir-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biology 2008; 10: 593-601. (Pubitemid 351627379)
232. Burk U, Schubert J, Wellner U, et al. A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep 2008; 9: 582-9. (Pubitemid 351772923)
233. Bueno MJ, Perez de Castro I, de Cedron MG, et al. Genetic and epigenetic silencing of micro RNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell 2008; 13: 496-506. (Pubitemid 351763902)
234. Greene SB, Herschkowitz JI, Rosen JM. The ups and downs ofmiR-205 Identifying the roles of miR-205 in mammary gland development and breast cancer. RNA Biol 2009; 7: 300-4.
235. Gottardo F, Liu CG, Ferracin M, et al. Micro-RNA profiling in kidney and bladder cancers. Urol Oncol Semin Orig Invest 2007; 25: 387-92. (Pubitemid 47362758)
236. Iorio MV, Casalini P, Piovan C, et al. micro RNA-205 regulates HER3 in human breast cancer. Cancer Res 2009; 69: 2195-200.
237. Greene SB, Gunaratne PH, Hammond SM, Rosen JM. A putative role for micro RNA-205 in mammary epithelial cell progenitors. J Cell Sci 2010; 123: 606-18.
238. Wu HL, Zhu SM, Mo YY. Suppression of cell growth and invasion by miR-205 in breast cancer. Cell Res 2009; 19: 439-48.
239. Zhang Z, Sun H, Dai H, et al. Micro RNA miR-210 modulates cellular response to hypoxia through the MYC antagonist MNT. Cell Cycle 2009; 8: 2756-68.
240. Fasanaro P, D'Alessandra Y, Di Stefano V, et al. Micro RNA-210 mod-ulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J Biol Chem 2008; 283: 15878-83.
241. Chen Z, Li Y, Zhang H, Huang P, Luthra R. Hypoxia-regulated micro-RNA-210 modulates mitochondrial function and decreases ISCU and COX10 expression. Oncogene 2010; 29: 4362-8.
242. Kim HW, Haider HK, Jiang SJ, Ashraf M. Ischemic preconditioning augments survival of stem cells via miR-210 expression by targeting caspase-8-associated protein 2. J Biol Chem 2009; 284: 33161-8.
243. Giannakakis A, Sandaltzopoulos R, Greshock J, et al. miR-210 links hypoxia with cell cycle regulation and is deleted in human epithelial ovarian cancer. Cancer Biol Ther 2008; 7: 255-64. (Pubitemid 351590433)
244. Mazar J, De Young K, Khaitan D. The regulation of miRNA-211 expres-sion and its role in melanoma cell invasiveness. PLoS One 2010; 5: e13779.
245. Lawrie CH, Soneji S, Marafioti T, et al. Microrna expression distinguishes between germinal center B cell-like and activated B cell-like subtypes of diffuse large B cell lymphoma. Int J Cancer 2007; 121: 1156-61. (Pubitemid 47101656)
246. Felli N, Fontana L, Pelosi E, et al. Micro RNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci USA 2005; 102: 18081-6 (Pubitemid 41798505)
247. le Sage C, Nagel R, Egan DA, et al. Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J 2007; 26: 3699-708. (Pubitemid 47236875)
248. Zhao JJ, Lin JH, Yang H, et al. Micro RNA-221/222 negatively regulates estrogen receptor alpha and is associated with tamoxifen resistance in breast cancer. J Biol Chem 2008; 283: 31079-86.
249. Garofalo M, Di Leva G, Romano G, et al. miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 down-regulation. Cancer Cell 2009; 16: 498-509.
250. Medina R, Zaidi SK, Liu CG, et al. Micro RNAs 221 and 222 bypass quiescence and compromise cell survival. Cancer Res 2008; 68: 2773-80. (Pubitemid 351556275)
251. Zhang CZ, Zhang JX, Zhang AL, et al. miR-221 and miR-222 target PUMA to induce cell survival in glioblastoma. Mol Cancer 2010; 9: 9.
252. Prueitt RL, Yi M, Hudson RS, et al. Expression of micro RNAs and protein-coding genes associated with perineural invasion in prostate cancer. Prostate 2008; 68: 1152-64.