Biomedical Papers, 2006 (vol. 150), issue 2

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2006, 150(2):205-215 | 10.5507/bp.2006.029

MicroRNA BIOGENESIS, FUNCTIONALITY AND CANCER RELEVANCE

Branislav Kusenda, Marek Mraz, Jiri Mayer, Sarka Pospisilova
Center of Molecular Biology and Gene Therapy, Department of Internal Medicine -, Hematooncology, University Hospital Brno, Černopolní 9, 625 00 Brno, Czech Republic

Background: MicroRNAs (miRNA) are small non-coding RNAs that negatively regulate gene expression in a sequence- specific manner. Post-transcriptional silencing of target genes by miRNA occurs either by specific cleavage of homologous mRNA or by specific inhibition of protein synthesis. MiRNAs are essential regulators of various processes such as proliferation, differentiation, development, cell death and interaction between virus and host cell.

Aim: The aim of this paper is to summarize the main findings from research on miRNA biogenesis, functionality and cancer relevance.

Method: A narrative literature review of all of the relevant papers known to the authors was conducted.

Results: Several human diseases including cancer are associated with aberrant regulation of miRNAs expression or deficiency in miRNA biogenesis. Analysis of miRNA expression signatures can serve as a valuable tool for cancer classification, diagnostics and prediction of tumor behavior.

Conclusions: There has been demonstrated a possibility to use these microRNA signatures for a specific cancer classification with potential predictive and therapeutic value. The known data provide evidence that microRNAs may open new ways for cancer diagnosis, prognosis estimation and therapy.

Keywords: MicroRNA, MiRNA, RNA interference, Cancer, CLL

Received: October 13, 2006; Accepted: November 30, 2006


References

  1. 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. Go to original source... Go to PubMed...
  2. Olsen PH, Ambros V. The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol. 1999; 216:671-80. Go to original source... Go to PubMed...
  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. Go to original source... Go to PubMed...
  4. Reinhart BJ, Slack FS, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 2000; 403:901-6. Go to original source... Go to PubMed...
  5. Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ. RAS is regulated by the let-7 microRNA family. Cell 2005; 120:635-47. Go to original source... Go to PubMed...
  6. Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda M, Maller B, Hayward DC, Ball EE, Degman B, Muller P, Spring J, Srinivasan A, Fisherman M, Finnerty J, Corbo J, Levine M, Davison E, Ruvkun G. Conservation across animal phylogeny of the sequence and temporal regulation of the 21 nucleotide let-7 heterochronic regulatory RNA. Nature 2000; 408:86-9. Go to original source... Go to PubMed...
  7. Lim PL, Glasner M, Yekta ES, Burge CB, Bartel DP. Vertebrate MicroRNA Genes. Science. 2003; 299:1540. Go to original source... Go to PubMed...
  8. He L, Hannon GJ. MicroRNAs: Small RNAs with a big role in gene regulation. Nature 2004; 5:522-31.
  9. Grosshans H, Slack FJ. Micro-RNAs: small is plentiful. The Journal of Cell Biology 2002; 156:17-22. Go to original source... Go to PubMed...
  10. Matzke M, Matzke AJM, Kooter JM. RNA:Guiding Gene Silencing. Science 2001; 293:1080-83. Go to original source... Go to PubMed...
  11. Bartel DP. MicroRNAs genomic, biogenesis, mechanism, and function. Cell 2004; 116:281-97. Go to original source... Go to PubMed...
  12. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004; 101:2999-3004. Go to original source... Go to PubMed...
  13. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM. A microRNA polycistron as a potential human oncogene. Nature 2005; 435:828-33. Go to original source... Go to PubMed...
  14. Ying SY, Lin SL. Intronic microRNAs. Biochemical and Biophysical Research Communications 2005; 326:515-20. Go to original source... Go to PubMed...
  15. Cai X, Hagedorn CH, Cullen, BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA 2004; 10:1957-66. Go to original source... Go to PubMed...
  16. Lee Y, Kim M, Han J, Yeom KH, Lee S, Back SH, Kim VN. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004; 23:4051-60. Go to original source... Go to PubMed...
  17. Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 2002; 21:4663-70. Go to original source... Go to PubMed...
  18. Gregory RI, Yan KP, Amuthan K, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R. The Microprocessor complex mediates the genesis of microRNAs. Nature 2004; 432:235-40. Go to original source... Go to PubMed...
  19. Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes and Development 2003; 17:3011-16. Go to original source... Go to PubMed...
  20. Hutvágner G, Zamore PD. A microRNA in a Multiple Turnover RNAi Enzyme Complex. Science 2002; 297:2056-60. Go to original source... Go to PubMed...
  21. Hammond SM, Bersnstein E, Beach D, Hannon GJ. An RNAdirected nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature 2000; 404:293-96. Go to original source... Go to PubMed...
  22. Martinez J, Tuschl T. RISC is a 5 phosphomonoester-producing RNA endonuclease. Genes Dev. 2004; 18:975-80. Go to original source... Go to PubMed...
  23. Zeng Y, Yi R, Cullen BR. MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. PNAS. 2003; 100:9779-84. Go to original source... Go to PubMed...
  24. Llave J, Tuschl T. RISC is a 5 hosphomonoester-producing RNA endonuclease. Genes and Development 2004; 18:975-80. Go to original source... Go to PubMed...
  25. Schwarz DS, Tomari Y, Zamore PD. The RNA-induced silencing complex is a Mg2+-dependent endonuclease. Curr Biol 2004; 14:787-91. Go to original source... Go to PubMed...
  26. Kern W, Kohlmann A, Wuchter C, Schnittger S, Schoch C, Mergenthaler S, Ratei R, Ludwig WD, Hiddemann W, Haferlach T. Correlation of protein expression and gene expression in acute leukemia, Cytometry 2003; 55B:29-36. Go to original source...
  27. Llave C, Kasschau KD, Rector MA, Carrington, JC. Endogenous and silencing-associated small RNAs in plants. Plant Cell 2002; 14:1605-19. Go to original source... Go to PubMed...
  28. Lai E, C. Micro RNAs are complementary to 3 UTR sequence motifs that mediate negative post-transcriptional regulation. Nature Genetics 2002; 30:363-4. Go to original source... Go to PubMed...
  29. Stark A, Brennecke J, Russell RB, Cohen SM. Identification of Drosophila MicroRNA targets. PLoS Biol. 2003; 1, E60. Go to original source... Go to PubMed...
  30. Wang XJ, Reyes JL, Chua NH, Gaasterland T. Prediction and identification of Arabidopsis thaliana microRNAs and their mRNA targets. Genome Biol. 2004; 5:R65. Go to original source... Go to PubMed...
  31. Ramesh SP, Suvendra A, Bhattacharyya SN, Artus CG, Zoller T, Cougot N, Basyuk E, Bertrand E, Filipowicz W. Inhibition of Translational Initiation by Let-7 MicroRNA in Human Cells. Science 2005; 309:1573-76. Go to original source... Go to PubMed...
  32. Doench JG, Petersen CP, Sharp PA. siRNAs can function as miRNAs. Genes & Development 2003; 17:438-42. Go to original source... Go to PubMed...
  33. Knight SW, Bass BL. A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science 2001; 293:2269-71. Go to original source... Go to PubMed...
  34. Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S, Ha I, Baillie DL, Fire A, Ruvkun G, Mello CC. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 2001; 106: 23-34. Go to original source... Go to PubMed...
  35. Giraldez AJ, Cinalli RM, Glasner ME, Enright AJ, Thomson JM, Baskerville S, Hammond SM, Bartel DP, Schier AF. MicroRNAs regulate brain morphogenesis in zebrafish. Science 2005; 308:833- 8. Go to original source... Go to PubMed...
  36. Giraldez AJ, Mishima Y, Rihel J, Grocock RJ, Van Dongen S, Inoue K, Enright AJ, Schier AF. Zebrafish MiR-430 Promotes Deadenylation and Clearance of Maternal mRNAs. Science 2006 Feb 16, 2006 [Epub ahead of print]
  37. Xu P, Vernooy SY, Guo M, Hay BA. The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr Biol. 2003; 13:790-5. Go to original source... Go to PubMed...
  38. Houbaviy HB, Murray MF, Sharp PA. Embryonic stem cell-specific MicroRNAs. Dev Cell. 2003; 5:351-8. Go to original source... Go to PubMed...
  39. Krichevsky AM, King KS, Donahue CP, Khrapko K, Kosik KS. A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 2003; 9:1274-81. Go to original source... Go to PubMed...
  40. Liu CG, Calin GA, Meloon B, Gamliel N, Sevignani C, Ferracin M, Dumitru CD, Shimizu M, Zupo S, Dono M, Alder H, Bullrich F, Negrini M, Croce CM. An oligonucleotide microchip for genomewide microRNA profiling in human and mouse tissues. PNAS. 2004; 101:9740-4. Go to original source... Go to PubMed...
  41. Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol. 2004; 5, R13. Go to original source... Go to PubMed...
  42. Wassenegger M, Heimes S, Riedel L, Sanger HL. RNA-directed de novo methylation of genomic sequences in plants. Cell 1994; 76, 567-76. Go to original source... Go to PubMed...
  43. Grewal SIS, Rice JC. Regulation of heterochromatin by histone methylation and small RNAs. Current Opinion in Cell Biology 2004; 16:230-38. Go to original source... Go to PubMed...
  44. Volpe TA, Kidner C, Hall IM, Teng G, Grewal SI, Martienssen RA. Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 2002; 297:1818-9. Go to original source... Go to PubMed...
  45. Hall IH, Shankaranarayana GD, Noma K, Ayoub N, Cohen A, Grewal SI. Establishment and maintenance of a heterochromatin domain. Science 2002; 297:2215-8. Go to original source... Go to PubMed...
  46. Sullivan CS, Ganem D. MicroRNAs and viral infection. Mol Cell. 2005; 20:3-7. Go to original source... Go to PubMed...
  47. Li HW, Ding SW. Antiviral silencing in animals. FEBS Lett. 2005; 579:5965-73. Go to original source... Go to PubMed...
  48. Christopher S, Sullivan CS, Grundhoff AT, Tevethia S, Pipas JM, Ganem D. SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells. Nature 2005; 435:682-86. Go to original source... Go to PubMed...
  49. Pfeffer S, Zavolan M, Grässer FA, Chien M, Russo JJ, Ju J, John B, Enright AJ, Marks D, Sander C, Tuschl T. Identification of Virus-Encoded MicroRNAs. Science 2004; 304:734-6. Go to original source... Go to PubMed...
  50. Dunn W, Trang P, Zhong Q, Yang E, Belle C, Liu F. Human cytomegalovirus expresses novel microRNAs during productive viral infection. Cellular Microbiology 2005; 7:1684-95. Go to original source... Go to PubMed...
  51. Grey F, Antoniewicz A, Allen E, Saugstad J, McShea A, Carrington JC, Nelson J. Identification and Characterization of Human Cytomegalovirus-Encoded MicroRNAs. J.Virol. 2005; 79:12095- 99. Go to original source... Go to PubMed...
  52. Bennasser Y, Le SY, Yeung M L, Jeang K T. HIV-1 encoded candidate micro-RNAs and their cellular targets. Retrovirology 2004; 1 (1):43. Go to original source... Go to PubMed...
  53. Cai X, Lu S, Zhang Z, Gonzalez CM, Damania B, Cullen BR. Kaposis sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells. PNAS. 2005; 102: 5570-5. Go to original source... Go to PubMed...
  54. Lecellier C, H, Dunoyer P, Arar K, Lehmann C, J, Eyquem S, Himber C, Saib A, Voinnet O. A cellular microRNA mediates antiviral defense in human cells. Science 2005; 308:557-60. Go to original source... Go to PubMed...
  55. Kasschau KD, Xie Z, Allen E, Llave C, Chapman E, J, Krizan KA, Carrington JC. P1/HC-Pro, a Viral Suppressor of RNA Silencing, Interferes with Arabidopsis Development and miRNA Function. Cell 2003; 4:205-17.
  56. Chen J, Li W, X, Xie D, Peng JR, Ding SW. Viral Virulence Protein Suppresses RNA Silencing-Mediated Defense but Upregulates the Role of MicroRNA in Host Gene Expression. The Plant Cell 2004; 16:1302-13. Go to original source... Go to PubMed...
  57. Chellallan P, Vanitharani R, Frauquet CM. MicroRNA-binding viral protein interferes with Arabidopsis development. PNAS. 2005; 102:10381-86. Go to original source... Go to PubMed...
  58. Lu S, Cullen BR. Adenovirus VA1 Noncoding RNA Can Inhibit Small Interfering RNA and MicroRNA Biogenesis. Journal of Virology 2004; 78:12868-76. Go to original source... Go to PubMed...
  59. Dostie J, Mourelatos Z, Yang M, Sharma A, Dreyfuss G. Numerous microRNPs in neuronal cells containing novel microRNAs. RNA 2003; 9:180-6. Go to original source... Go to PubMed...
  60. Ishizuka A, Siomi M, C, Siomi H. A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. Genes Dev. 2002; 16:2497-508. Go to original source... Go to PubMed...
  61. Shiohama A, Sasaki T, Noda N, 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. Go to original source... Go to PubMed...
  62. Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, Pfeffer S, Tuschl T, Rajewsky N, Rorsman P, Stoffel M. A pancreatic islet-specific microRNA regulates insulin secretion.Nature 2004; 432:226-30. Go to original source... Go to PubMed...
  63. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers.Nature 2005; 435:834-8. Go to original source... Go to PubMed...
  64. Bigoni R, Cuneo A, Roberti MG, Bardi A, Rigolin GM, Piva N, Scapoli G, Spanedda R, Negrini M, Bullrich F, Veronese ML, Croce CM, Castoldi G. Chromosome aberrations in atypical chronic lymphocytic leukemia: a cytogenetic and interphase cytogenetic study. Leukemia 1997; 11:1933-40. Go to original source... Go to PubMed...
  65. Desikan R, Barlogie B, Sawyer J, Ayers D, Tricot G, Badros A, Zangari M, Munshi NC, Anaissie E, Spoon D, Siegel D, Jagannath S, Vesole D, Epstein J, Shaughnessy J, Fassas A, Lim S, Roberson P, Crowley J. Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities. Blood 95: 2000; 4008-10.
  66. Dohner H, Stilgenbauer S, Dohner K, Bentz M, Lichter P. Chromosome aberrations in B-cell chronic lymphocytic leukemia: reassessment based on molecular cytogenetic analysis. J Mol Med. 1999; 77:266-81. Go to PubMed...
  67. Stilgenbauer S, Nickolenko J, Wilhelm J, Wolf S, Weitz S, Dohner K, Boehm T, Dohner H, Lichter P. Expressed sequences as candidates for a novel tumor suppressor gene at band 13q14 in Bcell chronic lymphocytic leukemia and mantle cell lymphoma. Oncogene 1998; 6:1891-7. Go to original source... Go to PubMed...
  68. Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, Rassenti L, Kipps T, Negrini M, Bullrich F, Croce CM. Frequent deletions and down-regulation of microRNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2002; 99:15524-9. Go to original source... Go to PubMed...
  69. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol. 2002; 12:735-9. Go to original source... Go to PubMed...
  70. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A. 2005; 102:13944-9. Go to original source... Go to PubMed...
  71. Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N, Dumitru CD, Shimizu M, Cimmino A, Zupo S, Dono M, DellAquila ML, Alder H, Rassenti L, Kipps TJ, Bullrich F, Negrini M, Croce CM. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A. 2004; 101: 11755-60. Go to original source... Go to PubMed...
  72. Juliusson G, Oscier DG, Fitchett M, Ross FM, Stockdill G, Mackie MJ, Parker AC, Castoldi GL, Guneo A, Knuutila S, Elonen E, Gahrton G. Prognostic subgroups in B-cell chronic lymphocytic leukemia defined by specific chromosomal abnormalities. N Engl J Med. 1990; 323:720-4. Go to original source... Go to PubMed...
  73. Oscier DG, Gardiner AC, Mould SJ, Glide S, Davis ZA, Ibbotson RE, Corcoran MM, Chapman RM, Thomas PW, Copplestone JA, Orchard JA, Hamblin TJ. Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors. Blood 2002; 100:1177-84. Go to PubMed...
  74. Orchard JA, Ibbotson RE, Davis Z, Wiestner A, Rosenwald A, Thomas PW, Hamblin TJ, Staudt LM, Oscier DG. ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet 2004; 363:105-11. Go to original source... Go to PubMed...
  75. Wiestner A, Rosenwald A, Barry TS, Wright G, Davis RE, Henrickson SE, Zhao H, Ibbotson RE, Orchard JA, Davis Z, Stetler-Stevenson M, Raffeld M, Arthur DC, Marti GE, Wilson WH, Hamblin TJ, Oscier DG, Staudt LM. ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile. Blood 2003; 101:4944-51. Go to original source... Go to PubMed...
  76. Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, Iorio MV, Visone R, Sever NI, Fabbri M, Iuliano R, Palumbo T, Pichiorri F, Roldo C, Garzon R, Sevignani C, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005; 353:1793-801. Go to original source... Go to PubMed...
  77. Eis PS, Tam W, Sun L, Chadburn A, Li Z, Gomez MF, Lund E, Dahlberg JE. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci U S A. 2005; 102: 3627-32. Go to original source... Go to PubMed...
  78. Knuutila S, Bjorkqvist AM, Autio K, Tarkkanen M, Wolf M, Monni O, Szymanska J, Larramendy ML, Tapper J, Pere H, El-Rifai W, Hemmer S, Wasenius VM, Vidgren V, Zhu Y. DNA copy number amplifications in human neoplasms: review of comparative genomic hybridization studies. Am J Pathol. 1998; 152:1107-23. Go to PubMed...
  79. Ota A, Tagawa H, Karnan S, Tsuzuki S, Karpas A, Kira S, Yoshida Y, Seto M. Identification and characterization of a novel gene, C13orf25, as a target for 13q31-q32 amplification in malignant lymphoma. Cancer Res. 2004; 64:3087-95. Go to original source... Go to PubMed...
  80. ODonnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2005; 435:839-43. Go to original source... Go to PubMed...
  81. Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K, Tomida S, Yatabe Y, Kawahara K, Sekido Y, Takahashi T. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res. 2005; 65:9628-32. Go to original source... Go to PubMed...
  82. Gauwerky CE, Huebner K, Isobe M, Nowell PC, Croce CM. Activation of MYC in a masked t(8;17) translocation results in an aggressive B-cell leukemia. Proc Natl Acad Sci U S A. 1989; 86:8867-71. Go to original source... Go to PubMed...
  83. Chen C, Z, Li L, Lodish HF, Bartel DP. MicroRNAs modulate hematopoietic lineage differentiation. Science 2004; 303:83-6. Go to original source... Go to PubMed...
  84. 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; 1:882-91. Go to PubMed...
  85. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Menard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005; 65:7065-70. Go to original source... Go to PubMed...
  86. Negrini M, Rasio D, Hampton GM, Sabbioni S, Rattan S, Carter SL, Rosenberg AL, Schwartz GF, Shiloh Y, Cavenee WK. Definition and refinement of chromosome 11 regions of loss of heterozygosity in breast cancer: identification of a new region at 11q23.3. Cancer Res. 1995; 55:3003-7. Go to PubMed...
  87. Rasio D, Negrini M, Manenti G, Dragani TA, Croce CM. Loss of heterozygosity at chromosome 11q in lung adenocarcinoma: identification of three independent regions. Cancer Res. 1995; 55:3988-91. Go to PubMed...
  88. Lee YS, Kim HK, Chung S, Kim KS, Dutta A. Depletion of human micro-RNA miR-125b reveals that it is critical for the proliferation of differentiated cells but not for the down-regulation of putative targets during differentiation. J Biol Chem 2005; 280:16635-41. Go to original source... Go to PubMed...
  89. Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T, Takahashi T. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004; 64:3753-6. Go to original source... Go to PubMed...
  90. Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, Stephens RM, Okamoto A, Yokota J, Tanaka T, Calin GA, Liu CG, Croce CM, Harris CC. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006; 9:189-98. Go to original source... Go to PubMed...
  91. Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ. RAS is regulated by the let-7 microRNA family. Cell 2005; 120:635-47. Go to original source... Go to PubMed...
  92. Karube Y, Tanaka H, Osada H, Tomida S, Tatematsu Y, Yanagisawa K, Yatabe Y, Takamizawa J, Miyoshi S, Mitsudomi T, Takahashi T. Reduced expression of Dicer associated with poor prognosis in lung cancer patients.Cancer Sci. 2005; 96:111-5. Go to original source... Go to PubMed...
  93. Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG. Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun. 2005; 334:1351-8. Go to original source... Go to PubMed...
  94. Chan JA, Krichevsky AM, Kosik KS. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005; 66: 6029-33. Go to original source... Go to PubMed...
  95. Holland EC. Gliomagenesis: genetic alterations and mouse models. Nat Rev Genet. 2001; 2:120-9. Go to original source... Go to PubMed...
  96. Zhu Y, Parada LF. The molecular and genetic basis of neurological tumours. Nat Rev Cancer. 2002; 2:616-26. Go to original source... Go to PubMed...
  97. Weber MJ. New human and mouse microRNA genes found by homology search. FEBS J. 2005; 272:59-73. Go to original source... Go to PubMed...