Biopolym. Cell. 2007; 23(6):467-482.
MicroRNA: from fundamental research to their application
1Shirina T. V., 1Bobrovskaya M. T., 1Kozlov E. A.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680


MicroRNAs (miRs) are small non-protein-encoding RNAs of 20–30 nucleotides long. In eukaryotic cells miRs play the role of bioregulators of gene expression through the mechanisms of translation repression/modulation. Here we both familiarize the readers with miRs biogenesis, functioning mechanisms, and strategy of their discovery and present the list of biological processes, regulated by miRs. We also list the publications, dedicated to miRs role in human pathologies (carcinogenesis in particular) and their application for marking, prevention, diagnostics, and therapy of cancer.
Keywords: microRNA, biogenesis, expression profile, bioinformatic, microRNA-prediction, bioregulation, carcinogenesis, therapy


[1] Pasquinelli AE. Demystifying small RNA pathways. Dev Cell. 2006;10(4):419-24.
[2] Plasterk RH. RNA silencing: the genome's immune system. Science. 2002;296(5571):1263-5.
[3] Zamore PD. Ancient pathways programmed by small RNAs. Science. 2002;296(5571):1265-9.
[4] Matzke MA, Birchler JA. RNAi-mediated pathways in the nucleus. Nat Rev Genet. 2005;6(1):24-35.
[5] Zhao Y, Srivastava D. A developmental view of microRNA function. Trends Biochem Sci. 2007;32(4):189-97.
[6] Zhang B, Wang Q, Pan X. MicroRNAs and their regulatory roles in animals and plants. J Cell Physiol. 2007;210(2):279-89.
[7] Wang Y, Stricker HM, Gou D, Liu L. MicroRNA: past and present. Front Biosci. 2007;12:2316-29.
[8] Scaria V, Hariharan M, Maiti S, Pillai B, Brahmachari SK. Host-virus interaction: a role for micro RNAs. Retrovirology. 2006; 3:68-76.
[9] Yu J, Wang F, Yang GH, Wang FL, Ma YN, Du ZW, Zhang JW. Human microRNA clusters: genomic organization and expression profile in leukemia cell lines. Biochem Biophys Res Commun. 2006;349(1):59-68.
[10] Li SC, Tang P, Lin WC. Intronic microRNA: discovery and biological implications. DNA Cell Biol. 2007;26(4):195-207.
[11] Kim YK, Kim VN. Processing of intronic microRNAs. EMBO J. 2007;26(3):775-83.
[12] Piriyapongsa J, Mari?o-Ram?rez L, Jordan IK. Origin and evolution of human microRNAs from transposable elements. Genetics. 2007;176(2):1323-37.
[13] Kluiver J, van den Berg A, de Jong D, Blokzijl T, Harms G, Bouwman E, Jacobs S, Poppema S, Kroesen BJ. Regulation of pri-microRNA BIC transcription and processing in Burkitt lymphoma. Oncogene. 2007;26(26):3769-76.
[14] Lee J, Li Z, Brower-Sinning R, John B. Regulatory circuit of human microRNA biogenesis. PLoS Comput Biol. 2007;3(4):e67.
[15] Fukao T, Fukuda Y, Kiga K, Sharif J, Hino K, Enomoto Y, Kawamura A, Nakamura K, Takeuchi T, Tanabe M. An evolutionarily conserved mechanism for microRNA-223 expression revealed by microRNA gene profiling. Cell. 2007;129(3):617-31.
[16] Shalgi R, Lieber D, Oren M, Pilpel Y. Global and local architecture of the mammalian microRNA-transcription factor regulatory network. PLoS Comput Biol. 2007;3(7):e131.
[17] Tsang J, Zhu J, van Oudenaarden A. MicroRNA-mediated feedback and feedforward loops are recurrent network motifs in mammals. Mol Cell. 2007;26(5):753-67.
[18] Xie ZR, Yang HT, Liu WC, Hwang MJ. The role of microRNA in the delayed negative feedback regulation of gene expression. Biochem Biophys Res Commun. 2007;358(3):722-6.
[19] Chuang JC, Jones PA. Epigenetics and microRNAs. Pediatr Res. 2007;61(5 Pt 2):24R-29R.
[20] Weber B, Stresemann C, Brueckner B, Lyko F. Methylation of human microRNA genes in normal and neoplastic cells. Cell Cycle. 2007;6(9):1001-5.
[21] Han L, Witmer PD, Casey E, Valle D, Sukumar S. DNA methylation regulates MicroRNA expression. Cancer Biol Ther. 2007;6(8):1284-8.
[22] Duan R, Pak C, Jin P. Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA. Hum Mol Genet. 2007;16(9):1124-31.
[23] Sethupathy P, Borel C, Gagnebin M, Grant GR, Deutsch S, Elton TS, Hatzigeorgiou AG, Antonarakis SE. Human microRNA-155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3' untranslated region: a mechanism for functional single-nucleotide polymorphisms related to phenotypes. Am J Hum Genet. 2007;81(2):405-13.
[24] Barnes MR, Deharo S, Grocock RJ, Brown JR, Sanseau P. The micro RNA target paradigm: a fundamental and polymorphic control layer of cellular expression. Expert Opin Biol Ther. 2007;7(9):1387-99.
[25] Amariglio N, Rechavi G. A-to-I RNA editing: a new regulatory mechanism of global gene expression. Blood Cells Mol Dis. 2007;39(2):151-5.
[26] Das AK, Carmichael GG. ADAR editing wobbles the microRNA world. ACS Chem Biol. 2007;2(4):217-20.
[27] Habig JW, Dale T, Bass BL. miRNA editing--we should have inosine this coming. Mol Cell. 2007;25(6):792-3.
[28] Kawahara Y, Zinshteyn B, Sethupathy P, Iizasa H, Hatzigeorgiou AG, Nishikura K. Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science. 2007;315(5815):1137-40.
[29] Liang H, Landweber LF. Hypothesis: RNA editing of microRNA target sites in humans? RNA. 2007;13(4):463-7.
[30] Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, Kim VN. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004;23(20):4051-60.
[31] Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281-97.
[32] Borchert GM, Lanier W, Davidson BL. RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol. 2006;13(12):1097-101.
[33] Zhou X, Ruan J, Wang G, Zhang W. Characterization and identification of microRNA core promoters in four model species. PLoS Comput Biol. 2007;3(3):e37.
[34] Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA. 2004;10(12):1957-66.
[35] Zeng Y, Cullen BR. Efficient processing of primary microRNA hairpins by Drosha requires flanking nonstructured RNA sequences. J Biol Chem. 2005;280(30):27595-603.
[36] Bashirullah A, Pasquinelli AE, Kiger AA, Perrimon N, Ruvkun G, Thummel CS. Coordinate regulation of small temporal RNAs at the onset of Drosophila metamorphosis. Dev Biol. 2003;259(1):1-8.
[37] Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science. 2001;294(5543):858-62.
[38] Mineno J, Okamoto S, Ando T, Sato M, Chono H, Izu H, Takayama M, Asada K, Mirochnitchenko O, Inouye M, Kato I. The expression profile of microRNAs in mouse embryos. Nucleic Acids Res. 2006;34(6):1765-71.
[39] Reinhart BJ, Weinstein EG, Rhoades MW, Bartel B, Bartel DP. MicroRNAs in plants. Genes Dev. 2002;16(13):1616-26.
[40] Qiu CX, Xie FL, Zhu YY, Guo K, Huang SQ, Nie L, Yang ZM. Computational identification of microRNAs and their targets in Gossypium hirsutum expressed sequence tags. Gene. 2007;395(1-2):49-61.
[41] 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(16):4622-9.
[42] Sohn SY, Bae WJ, Kim JJ, Yeom KH, Kim VN, Cho Y. Crystal structure of human DGCR8 core. Nat Struct Mol Biol. 2007;14(9):847-53.
[43] 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(1):106-20.
[44] Fukuda T, Yamagata K, Fujiyama S, Matsumoto T, Koshida I, Yoshimura K, Mihara M, Naitou M, Endoh H, Nakamura T, Akimoto C, Yamamoto Y, Katagiri T, Foulds C, Takezawa S, Kitagawa H, Takeyama K, O'Malley BW, Kato S. DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs. Nat Cell Biol. 2007;9(5):604-11.
[45] Chu CY, Rana TM. Translation repression in human cells by microRNA-induced gene silencing requires RCK/p54. PLoS Biol. 2006;4(7):e210.
[46] Jackson RJ, Standart N. How do microRNAs regulate gene expression? Sci STKE. 2007;2007(367):re1.
[47] Pillai RS, Bhattacharyya SN, Filipowicz W. Repression of protein synthesis by miRNAs: how many mechanisms? Trends Cell Biol. 2007;17(3):118-26.
[48] Ye X, Paroo Z, Liu Q. Functional anatomy of the Drosophila microRNA-generating enzyme. J Biol Chem. 2007;282(39):28373-8.
[49] Salzman DW, Shubert-Coleman J, Furneaux H. P68 RNA helicase unwinds the human let-7 microRNA precursor duplex and is required for let-7-directed silencing of gene expression. J Biol Chem. 2007;282(45):32773-9.
[50] Blevins T, Rajeswaran R, Shivaprasad PV, Beknazariants D, Si-Ammour A, Park HS, Vazquez F, Robertson D, Meins F Jr, Hohn T, Pooggin MM. Four plant Dicers mediate viral small RNA biogenesis and DNA virus induced silencing. Nucleic Acids Res. 2006;34(21):6233-46.
[51] Fujioka Y, Utsumi M, Ohba Y, Watanabe Y. Location of a possible miRNA processing site in SmD3/SmB nuclear bodies in Arabidopsis. Plant Cell Physiol. 2007;48(9):1243-53.
[52] Fang Y, Spector DL. Identification of nuclear dicing bodies containing proteins for microRNA biogenesis in living Arabidopsis plants. Curr Biol. 2007;17(9):818-23.
[53] Ro S, Park C, Young D, Sanders KM, Yan W. Tissue-dependent paired expression of miRNAs. Nucleic Acids Res. 2007;35(17):5944-53.
[54] Hwang HW, Wentzel EA, Mendell JT. A hexanucleotide element directs microRNA nuclear import. Science. 2007;315(5808):97-100.
[55] Politz JC, Zhang F, Pederson T. MicroRNA-206 colocalizes with ribosome-rich regions in both the nucleolus and cytoplasm of rat myogenic cells. Proc Natl Acad Sci U S A. 2006;103(50):18957-62.
[56] Long D, Lee R, Williams P, Chan CY, Ambros V, Ding Y. Potent effect of target structure on microRNA function. Nat Struct Mol Biol. 2007;14(4):287-94.
[57] Majoros WH, Ohler U. Spatial preferences of microRNA targets in 3' untranslated regions. BMC Genomics. 2007;8:152.
[58] Hon LS, Zhang Z. The roles of binding site arrangement and combinatorial targeting in microRNA repression of gene expression. Genome Biol. 2007;8(8):R166.
[59] Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, Bartel DP. MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell. 2007;27(1):91-105.
[60] Wang B, Love TM, Call ME, Doench JG, Novina CD. Recapitulation of short RNA-directed translational gene silencing in vitro. Mol Cell. 2006;22(4):553-60.
[61] Rajewsky N. microRNA target predictions in animals. Nat Genet. 2006;38 Suppl:S8-13.
[62] Brennecke J, Stark A, Russell RB, Cohen SM. Principles of microRNA-target recognition. PLoS Biol. 2005;3(3):e85.
[63] He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5(7):522-31.
[64] Meister G. miRNAs get an early start on translational silencing. Cell. 2007;131(1):25-8.
[65] Nilsen TW. Mechanisms of microRNA-mediated gene regulation in animal cells. Trends Genet. 2007;23(5):243-9.
[66] Thermann R, Hentze MW. Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation. Nature. 2007;447(7146):875-8.
[67] Kiriakidou M, Tan GS, Lamprinaki S, De Planell-Saguer M, Nelson PT, Mourelatos Z. An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell. 2007;129(6):1141-51.
[68] Mathonnet G, Fabian MR, Svitkin YV, Parsyan A, Huck L, Murata T, Biffo S, Merrick WC, Darzynkiewicz E, Pillai RS, Filipowicz W, Duchaine TF, Sonenberg N. MicroRNA inhibition of translation initiation in vitro by targeting the cap-binding complex eIF4F. Science. 2007;317(5845):1764-7.
[69] Standart N, Jackson RJ. MicroRNAs repress translation of m7Gppp-capped target mRNAs in vitro by inhibiting initiation and promoting deadenylation. Genes Dev. 2007;21(16):1975-82.
[70] Petersen CP, Bordeleau ME, Pelletier J, Sharp PA. Short RNAs repress translation after initiation in mammalian cells. Mol Cell. 2006;21(4):533-42.
[71] Maroney PA, Yu Y, Fisher J, Nilsen TW. Evidence that microRNAs are associated with translating messenger RNAs in human cells. Nat Struct Mol Biol. 2006;13(12):1102-7.
[72] Nottrott S, Simard MJ, Richter JD. Human let-7a miRNA blocks protein production on actively translating polyribosomes. Nat Struct Mol Biol. 2006;13(12):1108-14.
[73] Eulalio A, Behm-Ansmant I, Schweizer D, Izaurralde E. P-body formation is a consequence, not the cause, of RNA-mediated gene silencing. Mol Cell Biol. 2007;27(11):3970-81.
[74] Chan SP, Slack FJ. microRNA-mediated silencing inside P-bodies. RNA Biol. 2006;3(3):97-100.
[75] Bagga S, Bracht J, Hunter S, Massirer K, Holtz J, Eachus R, Pasquinelli AE. Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell. 2005;122(4):553-63.
[76] Tang G, Reinhart BJ, Bartel DP, Zamore PD. A biochemical framework for RNA silencing in plants. Genes Dev. 2003;17(1):49-63.
[77] Axtell MJ, Jan C, Rajagopalan R, Bartel DP. A two-hit trigger for siRNA biogenesis in plants. Cell. 2006;127(3):565-77.
[78] Cai X, Sch?fer A, Lu S, Bilello JP, Desrosiers RC, Edwards R, Raab-Traub N, Cullen BR. Epstein-Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS Pathog. 2006;2(3):e23.
[79] Kim HK, Lee YS, Sivaprasad U, Malhotra A, Dutta A. Muscle-specific microRNA miR-206 promotes muscle differentiation. J Cell Biol. 2006;174(5):677-87.
[80] George AD, Tenenbaum SA. MicroRNA modulation of RNA-binding protein regulatory elements. RNA Biol. 2006;3(2):57-9.
[81] Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science. 2005;309(5740):1577-81.
[82] Leung AK, Sharp PA. microRNAs: a safeguard against turmoil? Cell. 2007;130(4):581-5.
[83] Sunkar R, Zhu JK. Novel and stress-regulated microRNAs and other small RNAs from Arabidopsis. Plant Cell. 2004;16(8):2001-19.
[84] Berezikov E, Cuppen E, Plasterk RH. Approaches to microRNA discovery. Nat Genet. 2006;38 Suppl:S2-7.
[85] Zhang B, Pan X, Wang Q, Cobb GP, Anderson TA. Computational identification of microRNAs and their targets. Comput Biol Chem. 2006;30(6):395-407.
[86] Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, Lao KQ, Livak KJ, Guegler KJ. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 2005;33(20):e179.
[87] Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M, Dreyfuss G. miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. Genes Dev. 2002;16(6):720-8.
[88] Wang H, Ach RA, Curry B. Direct and sensitive miRNA profiling from low-input total RNA. RNA. 2007;13(1):151-9.
[89] Einat P. Methodologies for high-throughput expression profiling of microRNAs. Methods Mol Biol. 2006;342:139-57.
[90] Sempere LF, Sokol NS, Dubrovsky EB, Berger EM, Ambros V. Temporal regulation of microRNA expression in Drosophila melanogaster mediated by hormonal signals and broad-Complex gene activity. Dev Biol. 2003;259(1):9-18.
[91] Zuker M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 2003;31(13):3406-15.
[92] Xue C, Li F, He T, Liu GP, Li Y, Zhang X. Classification of real and pseudo microRNA precursors using local structure-sequence features and support vector machine. BMC Bioinformatics. 2005;6:310.
[93] Lai EC, Tomancak P, Williams RW, Rubin GM. Computational identification of Drosophila microRNA genes. Genome Biol. 2003;4(7):R42.
[94] Lim LP, Lau NC, Weinstein EG, Abdelhakim A, Yekta S, Rhoades MW, Burge CB, Bartel DP. The microRNAs of Caenorhabditis elegans. Genes Dev. 2003;17(8):991-1008.
[95] Ng KL, Mishra SK. De novo SVM classification of precursor microRNAs from genomic pseudo hairpins using global and intrinsic folding measures. Bioinformatics. 2007;23(11):1321-30.
[96] Chaudhuri K, Chatterjee R. MicroRNA detection and target prediction: integration of computational and experimental approaches. DNA Cell Biol. 2007;26(5):321-37.
[97] Watanabe Y, Tomita M, Kanai A. Computational methods for microRNA target prediction. Methods Enzymol. 2007;427:65-86.
[98] Huang JC, Morris QD, Frey BJ. Bayesian inference of MicroRNA targets from sequence and expression data. J Comput Biol. 2007;14(5):550-63.
[99] Doran J, Strauss WM. Bio-informatic trends for the determination of miRNA-target interactions in mammals. DNA Cell Biol. 2007;26(5):353-60.
[100] Lindow M, Gorodkin J. Principles and limitations of computational microRNA gene and target finding. DNA Cell Biol. 2007;26(5):339-51.
[101] Yousef M, Jung S, Kossenkov AV, Showe LC, Showe MK. Na?ve Bayes for microRNA target predictions--machine learning for microRNA targets. Bioinformatics. 2007;23(22):2987-92.
[102] Mazi?re P, Enright AJ. Prediction of microRNA targets. Drug Discov Today. 2007;12(11-12):452-8.
[103] Helvik SA, Sn?ve O Jr, Saetrom P. Reliable prediction of Drosha processing sites improves microRNA gene prediction. Bioinformatics. 2007;23(2):142-9.
[104] Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294(5543):853-8.
[105] Perera RJ, Ray A. MicroRNAs in the search for understanding human diseases. BioDrugs. 2007;21(2):97-104.
[106] Ahmed FE. Role of miRNA in carcinogenesis and biomarker selection: a methodological view. Expert Rev Mol Diagn. 2007;7(5):569-603.
[107] Bennasser Y, Le SY, Yeung ML, Jeang KT. HIV-1 encoded candidate micro-RNAs and their cellular targets. Retrovirology. 2004;1:43.
[108] Burnside J, Bernberg E, Anderson A, Lu C, Meyers BC, Green PJ, Jain N, Isaacs G, Morgan RW. Marek's disease virus encodes MicroRNAs that map to meq and the latency-associated transcript. J Virol. 2006;80(17):8778-86.
[109] Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005;120(1):15-20.
[110] Bhattacharyya SN, Habermacher R, Martine U, Closs EI, Filipowicz W. Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell. 2006;125(6):1111-24.
[111] Yu Z, Jian Z, Shen SH, Purisima E, Wang E. Global analysis of microRNA target gene expression reveals that miRNA targets are lower expressed in mature mouse and Drosophila tissues than in the embryos. Nucleic Acids Res. 2007;35(1):152-64.
[112] Darnell DK, Kaur S, Stanislaw S, Konieczka JK, Yatskievych TA, Antin PB. MicroRNA expression during chick embryo development. Dev Dyn. 2006;235(11):3156-65.
[113] Chen C, Ridzon D, Lee CT, Blake J, Sun Y, Strauss WM. Defining embryonic stem cell identity using differentiation-related microRNAs and their potential targets. Mamm Genome. 2007;18(5):316-27.
[114] Puc?at M, Ballis A. Embryonic stem cells: from bench to bedside. Clin Pharmacol Ther. 2007;82(3):337-9.
[115] Wang Y, Medvid R, Melton C, Jaenisch R, Blelloch R. DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat Genet. 2007;39(3):380-5.
[116] Sempere LF, Cole CN, McPeek MA, Peterson KJ. The phylogenetic distribution of metazoan microRNAs: insights into evolutionary complexity and constraint. J Exp Zool B Mol Dev Evol. 2006;306(6):575-88.
[117] Zhang B, Pan X, Anderson TA. Identification of 188 conserved maize microRNAs and their targets. FEBS Lett. 2006;580(15):3753-62.
[118] Xia XG, Zhou H, Samper E, Melov S, Xu Z. Pol II-expressed shRNA knocks down Sod2 gene expression and causes phenotypes of the gene knockout in mice. PLoS Genet. 2006;2(1):e10.
[119] Song L, Tuan RS. MicroRNAs and cell differentiation in mammalian development. Birth Defects Res C Embryo Today. 2006;78(2):140-9.
[120] Min H, Chen CZ. Methods for analyzing microRNA expression and function during hematopoietic lineage differentiation. Methods Mol Biol. 2006;342:209-27.
[121] Chen Y, Stallings RL. Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis. Cancer Res. 2007;67(3):976-83.
[122] Raftopoulou M. microRNA signals cell fate. Nat Cell Biol. 2006;8(2):112.
[123] Yang JH, Han SJ, Yoon EK, Lee WS. 'Evidence of an auxin signal pathway, microRNA167-ARF8-GH3, and its response to exogenous auxin in cultured rice cells'. Nucleic Acids Res. 2006;34(6):1892-9.
[124] Carleton M, Cleary MA, Linsley PS. MicroRNAs and cell cycle regulation. Cell Cycle. 2007;6(17):2127-32.
[125] Ryan DG, Oliveira-Fernandes M, Lavker RM. MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity. Mol Vis. 2006;12:1175-84.
[126] Karali M, Peluso I, Marigo V, Banfi S. Identification and characterization of microRNAs expressed in the mouse eye. Invest Ophthalmol Vis Sci. 2007;48(2):509-15.
[127] Bland CS, Cooper TA. Micromanaging alternative splicing during muscle differentiation. Dev Cell. 2007;12(2):171-2.
[128] Oakley EJ, Van Zant G. Unraveling the complex regulation of stem cells: implications for aging and cancer. Leukemia. 2007;21(4):612-21.
[129] Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH, Feldmann G, Yamakuchi M, Ferlito M, Lowenstein CJ, Arking DE, Beer MA, Maitra A, Mendell JT. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell. 2007;26(5):745-52.
[130] Raver-Shapira N, Marciano E, Meiri E, Spector Y, Rosenfeld N, Moskovits N, Bentwich Z, Oren M. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell. 2007;26(5):731-43.
[131] Zhang B, Pan X, Cobb GP, Anderson TA. microRNAs as oncogenes and tumor suppressors. Dev Biol. 2007;302(1):1-12.
[132] Coller HA, Forman JJ, Legesse-Miller A. "Myc'ed messages": myc induces transcription of E2F1 while inhibiting its translation via a microRNA polycistron. PLoS Genet. 2007;3(8):e146.
[133] Mott JL, Kobayashi S, Bronk SF, Gores GJ. mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene. 2007;26(42):6133-40.
[134] le Sage C, Nagel R, Egan DA, Schrier M, Mesman E, Mangiola A, Anile C, Maira G, Mercatelli N, Ciafr? SA, Farace MG, Agami R. Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J. 2007;26(15):3699-708.
[135] Cui Q, Yu Z, Purisima EO, Wang E. Principles of microRNA regulation of a human cellular signaling network. Mol Syst Biol. 2006;2:46.
[136] Vadstrup S. The adaptation of TSH secretion to autonomy in non-toxic goiter may be based-on active regulation of set-point and sensitivity of central TSH-receptors, perhaps by the microRNA (MIR) gene. Med Hypotheses. 2006;67(3):588-91.
[137] Mehler MF, Mattick JS. Non-coding RNAs in the nervous system. J Physiol. 2006;575(Pt 2):333-41.
[138] Wu J, Xie X. Comparative sequence analysis reveals an intricate network among REST, CREB and miRNA in mediating neuronal gene expression. Genome Biol. 2006;7(9):R85.
[139] Kosik KS. The neuronal microRNA system. Nat Rev Neurosci. 2006;7(12):911-20.
[140] Makeyev EV, Zhang J, Carrasco MA, Maniatis T. The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell. 2007;27(3):435-48.
[141] Hengst U, Jaffrey SR. Function and translational regulation of mRNA in developing axons. Semin Cell Dev Biol. 2007;18(2):209-15.
[142] Ramkissoon SH, Mainwaring LA, Ogasawara Y, Keyvanfar K, McCoy JP Jr, Sloand EM, Kajigaya S, Young NS. Hematopoietic-specific microRNA expression in human cells. Leuk Res. 2006;30(5):643-7.
[143] Nervi C, Fazi F, Rosa A, Fatica A, Bozzoni I. Emerging role for microRNAs in acute promyelocytic leukemia. Curr Top Microbiol Immunol. 2007;313:73-84.
[144] Lawrie CH. MicroRNAs and haematology: small molecules, big function. Br J Haematol. 2007;137(6):503-12.
[145] Grivna ST, Pyhtila B, Lin H. MIWI associates with translational machinery and PIWI-interacting RNAs (piRNAs) in regulating spermatogenesis. Proc Natl Acad Sci U S A. 2006;103(36):13415-20.
[146] Cobb BS, Hertweck A, Smith J, O'Connor E, Graf D, Cook T, Smale ST, Sakaguchi S, Livesey FJ, Fisher AG, Merkenschlager M. A role for Dicer in immune regulation. J Exp Med. 2006;203(11):2519-27.
[147] Dahlberg JE, Lund E. Micromanagement during the innate immune response. Sci STKE. 2007;2007(387):pe25.
[148] Thai TH, Calado DP, Casola S, Ansel KM, Xiao C, Xue Y, Murphy A, Frendewey D, Valenzuela D, Kutok JL, Schmidt-Supprian M, Rajewsky N, Yancopoulos G, Rao A, Rajewsky K. Regulation of the germinal center response by microRNA-155. Science. 2007;316(5824):604-8.
[149] Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, van Dongen S, Grocock RJ, Das PP, Miska EA, Vetrie D, Okkenhaug K, Enright AJ, Dougan G, Turner M, Bradley A. Requirement of bic/microRNA-155 for normal immune function. Science. 2007;316(5824):608-11.
[150] Hobert O. miRNAs play a tune. Cell. 2007;131(1):22-4.
[151] Wu H, Neilson JR, Kumar P, Manocha M, Shankar P, Sharp PA, Manjunath N. miRNA profiling of na?ve, effector and memory CD8 T cells. PLoS One. 2007;2(10):e1020.
[152] Boutz PL, Chawla G, Stoilov P, Black DL. MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development. Genes Dev. 2007;21(1):71-84.
[153] Brueckner B, Stresemann C, Kuner R, Mund C, Musch T, Meister M, S?ltmann H, Lyko F. The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function. Cancer Res. 2007;67(4):1419-23.
[154] Lujambio A, Ropero S, Ballestar E, Fraga MF, Cerrato C, Seti?n F, Casado S, Suarez-Gauthier A, Sanchez-Cespedes M, Git A, Spiteri I, Das PP, Caldas C, Miska E, Esteller M. Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res. 2007;67(4):1424-9.
[155] Huppi K, Volfovsky N, Mackiewicz M, Runfola T, Jones TL, Martin SE, Stephens R, Caplen NJ. MicroRNAs and genomic instability. Semin Cancer Biol. 2007;17(1):65-73.
[156] Saetrom P, Sn?ve O Jr, Rossi JJ. Epigenetics and microRNAs. Pediatr Res. 2007;61(5 Pt 2):17R-23R.
[157] Kr?tzfeldt J, Stoffel M. MicroRNAs: a new class of regulatory genes affecting metabolism. Cell Metab. 2006;4(1):9-12.
[158] Mersey BD, Jin P, Danner DJ. Human microRNA (miR29b) expression controls the amount of branched chain alpha-ketoacid dehydrogenase complex in a cell. Hum Mol Genet. 2005;14(22):3371-7.
[159] Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, Watts L, Booten SL, Graham M, McKay R, Subramaniam A, Propp S, Lollo BA, Freier S, Bennett CF, Bhanot S, Monia BP. miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell Metab. 2006;3(2):87-98.
[160] Gauthier BR, Wollheim CB. MicroRNAs: 'ribo-regulators' of glucose homeostasis. Nat Med. 2006;12(1):36-8.
[161] Chiou TJ, Aung K, Lin SI, Wu CC, Chiang SF, Su CL. Regulation of phosphate homeostasis by MicroRNA in Arabidopsis. Plant Cell. 2006;18(2):412-21.
[162] Uney JB, Lightman SL. MicroRNAs and osmotic regulation. Proc Natl Acad Sci U S A. 2006;103(42):15278-9.
[163] Liang H, Li WH. MicroRNA regulation of human protein protein interaction network. RNA. 2007;13(9):1402-8.
[164] Duan R, Jin P. Identification of messenger RNAs and microRNAs associated with fragile X mental retardation protein. Methods Mol Biol. 2006;342:267-76.
[165] Car? A, Catalucci D, Felicetti F, Bonci D, Addario A, Gallo P, Bang ML, Segnalini P, Gu Y, Dalton ND, Elia L, Latronico MV, H?ydal M, Autore C, Russo MA, Dorn GW 2nd, Ellingsen O, Ruiz-Lozano P, Peterson KL, Croce CM, Peschle C, Condorelli G. MicroRNA-133 controls cardiac hypertrophy. Nat Med. 2007;13(5):613-8.
[166] Thum T, Galuppo P, Wolf C, Fiedler J, Kneitz S, van Laake LW, Doevendans PA, Mummery CL, Borlak J, Haverich A, Gross C, Engelhardt S, Ertl G, Bauersachs J. MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation. 2007;116(3):258-67.
[167] Xu C, Lu Y, Pan Z, Chu W, Luo X, Lin H, Xiao J, Shan H, Wang Z, Yang B. The muscle-specific microRNAs miR-1 and miR-133 produce opposing effects on apoptosis by targeting HSP60, HSP70 and caspase-9 in cardiomyocytes. J Cell Sci. 2007;120(Pt 17):3045-52.
[168] Jeyaseelan K, Herath WB, Armugam A. MicroRNAs as therapeutic targets in human diseases. Expert Opin Ther Targets. 2007;11(8):1119-29.
[169] van Rooij E, Olson EN. MicroRNAs: powerful new regulators of heart disease and provocative therapeutic targets. J Clin Invest. 2007;117(9):2369-76.
[170] Sayed D, Hong C, Chen IY, Lypowy J, Abdellatif M. MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res. 2007;100(3):416-24.
[171] O'Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A. 2007;104(5):1604-9.
[172] Rane S, Sayed D, Abdellatif M. MicroRNA with a MacroFunction. Cell Cycle. 2007;6(15):1850-5.
[173] Wu W, Sun M, Zou GM, Chen J. MicroRNA and cancer: Current status and prospective. Int J Cancer. 2007;120(5):953-60.
[174] Lee EJ, Gusev Y, Jiang J, Nuovo GJ, Lerner MR, Frankel WL, Morgan DL, Postier RG, Brackett DJ, Schmittgen TD. Expression profiling identifies microRNA signature in pancreatic cancer. Int J Cancer. 2007;120(5):1046-54.
[175] Xu W, Li JY. MicroRNA gene expression in malignant lymphoproliferative disorders. Chin Med J (Engl). 2007;120(11):996-9.
[176] Lawrie CH. MicroRNA expression in lymphoma. Expert Opin Biol Ther. 2007;7(9):1363-74.
[177] Giannakakis A, Coukos G, Hatzigeorgiou A, Sandaltzopoulos R, Zhang L. miRNA genetic alterations in human cancers. Expert Opin Biol Ther. 2007;7(9):1375-86.
[178] Subramanian S, Lui WO, Lee CH, Espinosa I, Nielsen TO, Heinrich MC, Corless CL, Fire AZ, van de Rijn M. MicroRNA expression signature of human sarcomas. Oncogene. 2008;27(14):2015-26.
[179] Blenkiron C, Goldstein LD, Thorne NP, Spiteri I, Chin SF, Dunning MJ, Barbosa-Morais NL, Teschendorff AE, Green AR, Ellis IO, Tavar? S, Caldas C, Miska EA. MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol. 2007;8(10):R214.
[180] Wurdinger T, Costa FF. Molecular therapy in the microRNA era. Pharmacogenomics J. 2007;7(5):297-304.
[181] Yeung ML, Bennasser Y, Jeang KT. miRNAs in the biology of cancers and viral infections. Curr Med Chem. 2007;14(2):191-7.
[182] Osada H, Takahashi T. MicroRNAs in biological processes and carcinogenesis. Carcinogenesis. 2007;28(1):2-12.
[183] Wijnhoven BP, Michael MZ, Watson DI. MicroRNAs and cancer. Br J Surg. 2007;94(1):23-30.
[184] Porkka KP, Pfeiffer MJ, Waltering KK, Vessella RL, Tammela TL, Visakorpi T. MicroRNA expression profiling in prostate cancer. Cancer Res. 2007;67(13):6130-5.
[185] Jay C, Nemunaitis J, Chen P, Fulgham P, Tong AW. miRNA profiling for diagnosis and prognosis of human cancer. DNA Cell Biol. 2007;26(5):293-300.
[186] Hernando E. microRNAs and cancer: role in tumorigenesis, patient classification and therapy. Clin Transl Oncol. 2007;9(3):155-60.
[187] Zhang W, Dahlberg JE, Tam W. MicroRNAs in tumorigenesis: a primer. Am J Pathol. 2007;171(3):728-38.
[188] Voorhoeve PM, Agami R. Classifying microRNAs in cancer: the good, the bad and the ugly. Biochim Biophys Acta. 2007;1775(2):274-82.
[189] Calin GA, Pekarsky Y, Croce CM. The role of microRNA and other non-coding RNA in the pathogenesis of chronic lymphocytic leukemia. Best Pract Res Clin Haematol. 2007;20(3):425-37.
[190] Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449(7163):682-8.
[191] Matsubara H, Takeuchi T, Nishikawa E, Yanagisawa K, Hayashita Y, Ebi H, Yamada H, Suzuki M, Nagino M, Nimura Y, Osada H, Takahashi T. Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. Oncogene. 2007;26(41):6099-105.
[192] Corsten MF, Miranda R, Kasmieh R, Krichevsky AM, Weissleder R, Shah K. MicroRNA-21 knockdown disrupts glioma growth in vivo and displays synergistic cytotoxicity with neural precursor cell delivered S-TRAIL in human gliomas. Cancer Res. 2007;67(19):8994-9000.
[193] Bottoni A, Zatelli MC, Ferracin M, Tagliati F, Piccin D, Vignali C, Calin GA, Negrini M, Croce CM, Degli Uberti EC. Identification of differentially expressed microRNAs by microarray: a possible role for microRNA genes in pituitary adenomas. J Cell Physiol. 2007;210(2):370-7.
[194] Pallante P, Visone R, Ferracin M, Ferraro A, Berlingieri MT, Troncone G, Chiappetta G, Liu CG, Santoro M, Negrini M, Croce CM, Fusco A. MicroRNA deregulation in human thyroid papillary carcinomas. Endocr Relat Cancer. 2006;13(2):497-508.
[195] Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, Prueitt RL, Yanaihara N, Lanza G, Scarpa A, Vecchione A, Negrini M, Harris CC, Croce CM. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103(7):2257-61.
[196] Liu W, Mao SY, Zhu WY. Impact of tiny miRNAs on cancers. World J Gastroenterol. 2007;13(4):497-502.
[197] Nairz K, Rottig C, Rintelen F, Zdobnov E, Moser M, Hafen E. Overgrowth caused by misexpression of a microRNA with dispensable wild-type function. Dev Biol. 2006;291(2):314-24.
[198] Weber F, Teresi RE, Broelsch CE, Frilling A, Eng C. A limited set of human MicroRNA is deregulated in follicular thyroid carcinoma. J Clin Endocrinol Metab. 2006;91(9):3584-91.
[199] Lee YS, Dutta A. MicroRNAs: small but potent oncogenes or tumor suppressors. Curr Opin Investig Drugs. 2006;7(6):560-4.
[200] Tam W, Dahlberg JE. miR-155/BIC as an oncogenic microRNA. Genes Chromosomes Cancer. 2006;45(2):211-2.
[201] 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(21):9628-32.
[202] Voorhoeve PM, le Sage C, Schrier M, Gillis AJ, Stoop H, Nagel R, Liu YP, van Duijse J, Drost J, Griekspoor A, Zlotorynski E, Yabuta N, De Vita G, Nojima H, Looijenga LH, Agami R. A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell. 2006;124(6):1169-81.
[203] Akao Y, Nakagawa Y, Naoe T. MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncol Rep. 2006;16(4):845-50.
[204] Yu SL, Chen HY, Yang PC, Chen JJ. Unique MicroRNA signature and clinical outcome of cancers. DNA Cell Biol. 2007;26(5):283-92.
[205] Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259-69.
[206] Kent OA, Mendell JT. A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes. Oncogene. 2006;25(46):6188-96.
[207] Hammond SM. MicroRNAs as oncogenes. Curr Opin Genet Dev. 2006;16(1):4-9.
[208] Hwang HW, Mendell JT. MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer. 2006;94(6):776-80.
[209] Jannot G, Simard MJ. Tumour-related microRNAs functions in Caenorhabditis elegans. Oncogene. 2006;25(46):6197-201.
[210] Calin GA, Croce CM. Genomics of chronic lymphocytic leukemia microRNAs as new players with clinical significance. Semin Oncol. 2006;33(2):167-73.
[211] Hossain A, Kuo MT, Saunders GF. Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA. Mol Cell Biol. 2006;26(21):8191-201.
[212] Hwang HW, Mendell JT. MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer. 2007;96 Suppl:R40-4.
[213] Tricoli JV, Jacobson JW. MicroRNA: Potential for Cancer Detection, Diagnosis, and Prognosis. Cancer Res. 2007;67(10):4553-5.
[214] Perron MP, Boissonneault V, Gobeil LA, Ouellet DL, Provost P. Regulatory RNAs: future perspectives in diagnosis, prognosis, and individualized therapy. Methods Mol Biol. 2007;361:311-26.
[215] Negrini M, Ferracin M, Sabbioni S, Croce CM. MicroRNAs in human cancer: from research to therapy. J Cell Sci. 2007;120(Pt 11):1833-40.
[216] Esau CC, Monia BP. Therapeutic potential for microRNAs. Adv Drug Deliv Rev. 2007;59(2-3):101-14.
[217] Jeyaseelan K, Herath WB, Armugam A. MicroRNAs as therapeutic targets in human diseases. Expert Opin Ther Targets. 2007;11(8):1119-29.
[218] Bandres E, Agirre X, Ramirez N, Zarate R, Garcia-Foncillas J. MicroRNAs as cancer players: potential clinical and biological effects. DNA Cell Biol. 2007;26(5):273-82.
[219] Kr?tzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M. Silencing of microRNAs in vivo with 'antagomirs'. Nature. 2005;438(7068):685-9.
[220] ?rom UA, Kauppinen S, Lund AH. LNA-modified oligonucleotides mediate specific inhibition of microRNA function. Gene. 2006;372:137-41.
[221] Naguibneva I, Ameyar-Zazoua M, Nonne N, Polesskaya A, Ait-Si-Ali S, Groisman R, Souidi M, Pritchard LL, Harel-Bellan A. An LNA-based loss-of-function assay for micro-RNAs. Biomed Pharmacother. 2006;60(9):633-8.
[222] Tsuda N, Ishiyama S, Li Y, Ioannides CG, Abbruzzese JL, Chang DZ. Synthetic microRNA designed to target glioma-associated antigen 1 transcription factor inhibits division and induces late apoptosis in pancreatic tumor cells. Clin Cancer Res. 2006;12(21):6557-64.
[223] Davis S, Lollo B, Freier S, Esau C. Improved targeting of miRNA with antisense oligonucleotides. Nucleic Acids Res. 2006;34(8):2294-304.
[224] Mattes J, Yang M, Foster PS. Regulation of microRNA by antagomirs: a new class of pharmacological antagonists for the specific regulation of gene function? Am J Respir Cell Mol Biol. 2007;36(1):8-12.
[225] Sn?ve O Jr, Rossi JJ. Toxicity in mice expressing short hairpin RNAs gives new insight into RNAi. Genome Biol. 2006;7(8):231.
[226] Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, Davis CR, Marion P, Salazar F, Kay MA. Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways. Nature. 2006;441(7092):537-41.
[227] John M, Constien R, Akinc A, Goldberg M, Moon YA, Spranger M, Hadwiger P, Soutschek J, Vornlocher HP, Manoharan M, Stoffel M, Langer R, Anderson DG, Horton JD, Koteliansky V, Bumcrot D. Effective RNAi-mediated gene silencing without interruption of the endogenous microRNA pathway. Nature. 2007;449(7163):745-7.
[228] Jain KK. Commercial potential of RNAi. Mol Biosyst. 2006;2(11):523-6.