Genetic variation in microRNA networks: The implications for cancer research

Nature Reviews Cancer

Volumn 10, Issue 6, 2010, Pages 389-402

  Ryan, Bríd M ^a   Robles, Ana I ^a   Harris, Curtis C ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BRCA2 PROTEIN; MICRORNA;

ALLELE; AMINO ACID SEQUENCE; BINDING SITE; BLADDER CANCER; BREAST CANCER; CANCER GENETICS; CANCER RESEARCH; CANCER RISK; CASE CONTROL STUDY; EPIGENETICS; ESOPHAGUS CANCER; GENE EXPRESSION; GENETIC LINKAGE; GENETIC VARIABILITY; GENOTYPE; GLIOMA; HUMAN; LIVER CELL CARCINOMA; LUNG CANCER; MEDICAL INFORMATION; METHODOLOGY; NONHUMAN; POLYADENYLATION; PRIORITY JOURNAL; PROGNOSIS; REVIEW; RNA SPLICING; RNA STRUCTURE; SINGLE NUCLEOTIDE POLYMORPHISM;

ALTERNATIVE SPLICING; ANIMALS; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE REGULATORY NETWORKS; HUMANS; MICRORNAS; NEOPLASMS; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 77952918274     PISSN: 1474175X     EISSN: 14741768     Source Type: Journal    
DOI: 10.1038/nrc2867     Document Type: Review

References (164)

1. Frazer, K. A. et al. A second generation human haplotype map of over 3.1 million SNPs. Nature 449, 851-861 (2007).
2. Kan, Y. W. & Dozy, A. M. Polymorphism of DNA sequence adjacent to human beta-globin structural gene: relationship to sickle mutation. Proc. Natl Acad. Sci. USA 75, 5631-5635 (1978).
3. International HapMap Consortium. A haplotype map of the human genome. Nature 437, 1299-1320 (2005).
4. Bartel, B. MicroRNAs directing siRNA biogenesis. Nature Struct. Mol. Biol. 12, 569-571 (2005).
5. Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 11 6, 281-297 (2004).
6. Vasudevan, S., Tong, Y. & Steitz, J. A. Switching from repression to activation: microRNAs can up-regulate translation. Science 318, 1931-1934 (2007).
7. Kim, V. N. MicroRNA biogenesis: coordinated cropping and dicing. Nature Rev. Mol. Cell Biol. 6, 376-385 (2005).
8. Lai, E. C. Micro RNAs are complementary to 3' UTR sequence motifs that mediate negative post-transcriptional regulation. Nature Genet. 30, 363-364 (2002).
9. Lewis, B. P., Shih, I. H., Jones-Rhoades, M. W., Bartel, D. P. & Burge, C. B. Prediction of mammalian microRNA targets. Cell 11 5, 787-798 (2003).
10. Stark, A., Brennecke, J., Russell, R. B. & Cohen, S. M. Identification of Drosophila MicroRNA targets. PLoS Biol. 1, E60 (2003).
11. Grimson, A. et al. MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol. Cell 27, 91-105 (2007).
12. Hobert, O. Common logic of transcription factor and microRNA action. Trends Biochem. Sci. 29, 462-468 (2004).
13. Krek, A. et al. Combinatorial microRNA target predictions. Nature Genet. 37, 495-500 (2005).
14. Hon, L. S. & Zhang, Z. The roles of binding site arrangement and combinatorial targeting in microRNA repression of gene expression. Genome Biol. 8, R166 (2007).
15. Kumar, M. S., Lu, J., Mercer, K. L., Golub, T. R. & Jacks, T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nature Genet. 39, 673-677 (2007).
16. Lu, J. et al. MicroRNA expression profiles classify human cancers. Nature 435, 834-838 (2005).
17. Garzon, R., Calin, G. A. & Croce, C. M. MicroRNAs in cancer. Annu. Rev. Med. 60, 167-179 (2009).
18. Kent, O. A. & Mendell, J. T. A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes. Oncogene 25, 6188-6196 (2006).
19. Esquela-Kerscher, A. & Slack, F. J. Oncomirs\microRNAs with a role in cancer. Nature Rev. Cancer 6, 259-269 (2006).
20. Fabbri, M., Ivan, M., Cimmino, A., Negrini, M. & Calin, G. A. Regulatory mechanisms of microRNAs involvement in cancer. Expert Opin. Biol. Ther. 7, 1009-1019 (2007).
21. Calin, G. A. 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 99, 15524-15529 (2002).
22. Calin, G. A. et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc. Natl Acad. Sci. USA 101, 2999-3004 (2004).
23. Sevignani, C. et al. MicroRNA genes are frequently located near mouse cancer susceptibility loci. Proc. Natl Acad. Sci. USA 104, 8017-8022 (2007).
24. Yang, W. et al. Modulation of microRNA processing and expression through RNA editing by ADAR deaminases. Nature Struct. Mol. Biol. 13, 13-21 (2006).
25. Seitz, H., Ghildiyal, M. & Zamore, P. D. Argonaute loading improves the 5' precision of both MicroRNAs and their miRNA* strands in flies. Curr. Biol. 18, 147-151 (2008).
26. Abelson, J. F. et al. Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science 310, 317-320 (2005).
27. Saunders, M. A., Liang, H. & Li, W. H. Human polymorphism at microRNAs and microRNA target sites. Proc. Natl Acad. Sci. USA 104, 3300-3305 (2007). (Pubitemid 46364154)
28. Duan, R., Pak, C. & Jin, P. Single nucleotide polymorphism associated with mature miR-125a alters the processing of pri-miRNA. Hum. Mol. Genet. 16, 1124-1131 (2007).
29. Wu, M. et al. Genetic variations of microRNAs in human cancer and their effects on the expression of miRNAs. Carcinogenesis 29, 1710-1716 (2008).
30. Chen, K. & Rajewsky, N. Natural selection on human microRNA binding sites inferred from SNP data. Nature Genet. 38, 1452-1456 (2006).
31. Iwai, N. & Naraba, H. Polymorphisms in human pre-miRNAs. Biochem. Biophys. Res. Commun. 331, 1439-1444 (2005).
32. Calin, G. A. et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N. Engl. J. Med. 353, 1793-1801 (2005).
33. Raveche, E. S. et al. Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice. Blood 109, 5079-5086 (2007).
34. Yazici, H. et al. Investigation of the miR16-11 (C > T) + 7 substitution in seven different types of cancer from three ethnic groups. J. Oncol. 2009 (doi:10.1155/2009/827532).
35. Yang, H. et al. Evaluation of genetic variants in microRNA-related genes and risk of bladder cancer. Cancer Res. 68, 2530-2537 (2008).
36. Clague, J. et al. Genetic variation in MicroRNA genes and risk of oral premalignant lesions. Mol. Carcinog. 49, 183-189 (2009).
37. Y e, Y. et al. Genetic variations in microRNA-related genes are novel susceptibility loci for esophageal cancer risk. Cancer Prev. Res. (Phila. Pa.) 1, 460-469 (2008).
38. Hu, Z. et al. Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women. Hum. Mutat. 30, 79-84 (2009).
39. Tian, T. et al. A functional genetic variant in microRNA-196a2 is associated with increased susceptibility of lung cancer in Chinese. Cancer Epidemiol. Biomarkers Prev. 18, 1183-1187 (2009).
40. Hoffman, A. E. et al. microRNA miR-196a-2 and breast cancer: a genetic and epigenetic association study and functional analysis. Cancer Res. 69, 5970-5977 (2009).
41. Peng, S. et al. Association of MicroRNA-196a-2 Gene Polymorphism with Gastric Cancer Risk in a Chinese Population. Dig Dis. Sci. 16 Oct 2009 (doi:10.1007/s10620-009-1007-x).
42. Gottwein, E., Cai, X. & Cullen, B. R. Expression and function of microRNAs encoded by Kaposi's sarcoma-associated herpesvirus. Cold Spring Harb. Symp. Quant. Biol. 71, 357-364 (2006).
43. Hu, Z. et al. Genetic variants of miRNA sequences and non-small cell lung cancer survival. J. Clin. Invest. 11 8, 2600-2608 (2008).
44. Yang, R. et al. A genetic variant in the pre-miR-27a oncogene is associated with a reduced familial breast cancer risk. Breast Cancer Res. Treat 17 Nov 2009 (doi: 10.1007/s10549-009-0633-5).
45. Kontorovich, T., Levy, A., Korostishevsky, M., Nir, U. & Friedman, E. SNPs in miRNA binding sites and miRNA genes as breast/ovarian cancer risk modifiers in Jewish high risk women. Int. J. Cancer 30 Nov 2009 [epub ahead of print].
46. Zeng, Y. & Cullen, B. R. Efficient processing of primary microRNA hairpins by Drosha requires flanking nonstructured RNA sequences. J. Biol. Chem. 280, 27595-27603 (2005).
47. Piskounova, E. et al. Determinants of microRNA processing inhibition by the developmentally regulated RNA-binding protein Lin28. J. Biol. Chem. 283, 21310-21314 (2008).
48. Newman, M. A., Thomson, J. M. & Hammond, S. M. Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing. RNA 14, 1539-1549 (2008).
49. Yang, J. et al. Analysis of sequence variations in 59 microRNAs in hepatocellular carcinomas. Mutat. Res. 638, 205-209 (2008).
50. Jazdzewski, K. et al. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc. Natl Acad. Sci. USA 105, 7269-7274 (2008).
51. Jazdzewski, K. et al. Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer. Proc. Natl Acad. Sci. USA 106, 1502-1505 (2009).
52. Xu, B. et al. A functional polymorphism in Pre-miR-146a gene is associated with prostate cancer risk and mature miR-146a expression in vivo. Prostate 70, 467-472 (2009).
53. Xu, T. et al. A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis 29, 2126-2131 (2008).
54. Shen, J. et al. A functional polymorphism in the miR-146a gene and age of familial breast/ovarian cancer diagnosis. Carcinogenesis 29, 1963-1966 (2008).
55. Taganov, K. D., Boldin, M. P., Chang, K. J. & Baltimore, D. NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc. Natl Acad. Sci. USA 103, 12481-12486 (2006).
56. Perry, M. M. et al. Rapid changes in microRNA-146a expression negatively regulate the IL-1β-induced inflammatory response in human lung alveolar epithelial cells. J. Immunol. 180, 5689-5698 (2008).
57. Quach, H. et al. Signatures of purifying and local positive selection in human miRNAs. Am. J. Hum. Genet. 84, 316-327 (2009).
58. Chanock, S. J. et al. Replicating genotype-phenotype associations. Nature 447, 655-660 (2007).
59. Sethupathy, P. & Collins, F. S. MicroRNA target site polymorphisms and human disease. Trends Genet. 24, 489-497 (2008).
60. Jensen, K. P. et al. A common polymorphism in serotonin receptor 1B mRNA moderates regulation by miR-96 and associates with aggressive human behaviors. Mol. Psychiatry 14, 381-399 (2009).
61. Martin, M. M., Lee, E. J., Buckenberger, J. A., Schmittgen, T. D. & Elton, T. S. MicroRNA-155 regulates human angiotensin II type 1 receptor expression in fibroblasts. J. Biol. Chem. 281, 18277-18284 (2006).
62. Sethupathy, P. et al. 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. 81, 405-413 (2007).
63. Tan, Z. et al. Allele-specific targeting of microRNAs to HLA-G and risk of asthma. Am. J. Hum. Genet. 81, 829-834 (2007).
64. Tan, S. et al. Retained introns increase putative microRNA targets within 3' UTRs of human mRNA. FEBS Lett. 581, 1081-1086 (2007).
65. Lv, K. et al. Allele-specific targeting of hsa-miR-657 to human IGF2R creates a potential mechanism underlying the association of ACAA-insertion/ deletion polymorphism with type 2 diabetes. Biochem. Biophys. Res. Commun. 374, 101-105 (2008).
66. Tay, Y. et al. Insights into the regulation of a common variant of HMGA2 associated with human height during embryonic development. Stem Cell Rev. 5, 328-333 (2009).
67. Weedon, M. N. et al. A common variant of HMGA2 is associated with adult and childhood height in the general population. Nature Genet. 39, 1245-1250 (2007).
68. Conner, T. S. et al. Functional polymorphisms in the serotonin 1B receptor gene (HTR1B) predict self-reported anger and hostility among young men. Am. J. Med. Genet. B Neuropsychiatr. Genet. 153B, 67-78 (2010).
69. Huang, W. & Li, M. D. Differential allelic expression of dopamine D1 receptor gene (DRD1) is modulated by microRNA miR-504. Biol. Psychiatry 65, 702-705 (2009).
70. Cargill, E. J., Nissing, N. J. & Grosz, M. D. Single nucleotide polymorphisms concordant with the horned/polled trait in Holsteins. BMC Res. Notes 1, 128 (2008).
71. Clop, A. et al. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nature Genet. 38, 813-818 (2006).
72. Johnson, S. M. et al. RAS is regulated by the let-7 microRNA family. Cell 120, 635-647 (2005).
73. Takamizawa, J. et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 64, 3753-3756 (2004).
74. Chin, L. J. et al. A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk. Cancer Res. 68, 8535-8540 (2008).
75. Nelson, H. H. et al. KRAS mutation, KRAS-LCS6 polymorphism, and non-small cell lung cancer. Lung Cancer 24 Oct 2009 (doi:10.1016/j. lungcan.2009.09.008).
76. Heo, I. et al. Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA. Mol. Cell 32, 276-284 (2008).
77. Viswanathan, S. R., Daley, G. Q. & Gregory, R. I. Selective blockade of microRNA processing by Lin28. Science 320, 97-100 (2008).
78. Christensen, B. C. et al. A let-7 microRNA-binding site polymorphism in the KRAS 3' UTR is associated with reduced survival in oral cancers. Carcinogenesis 30, 1003-1007 (2009).
79. Landi, D. et al. Polymorphisms within micro-RNA-binding sites and risk of sporadic colorectal cancer. Carcinogenesis 29, 579-584 (2008).
80. Freeman, G. J. et al. B7-1 and B7-2 do not deliver identical costimulatory signals, since B7-2 but not B7-1 preferentially costimulates the initial production of IL-4. Immunity 2, 523-532 (1995).
81. Georges, M. et al. Polymorphic microRNA-target interactions: a novel source of phenotypic variation. Cold Spring Harb. Symp. Quant. Biol. 71, 343-350 (2006).
82. Yu, Z. et al. Aberrant allele frequencies of the SNPs located in microRNA target sites are potentially associated with human cancers. Nucleic Acids Res. 35, 4535-4541 (2007).
83. Song, F. et al. An miR-502-binding site single-nucleotide polymorphism in the 3'-untranslated region of the SET8 gene is associated with early age of breast cancer onset. Clin. Cancer Res. 15, 6292-6300 (2009).
84. Landi, D., Gemignani, F., Barale, R. & Landi, S. A catalog of polymorphisms falling in microRNA-binding regions of cancer genes. DNA Cell Biol. 27, 35-43 (2008).
85. Gao, Y. et al. An insertion/deletion polymorphism at miRNA-122-binding site in the interleukin-1alpha 3' untranslated region confers risk for hepatocellular carcinoma. Carcinogenesis 30, 2064-2069 (2009).
86. Saetrom, P. et al. A risk variant in an miR-125b binding site in BMPR1B is associated with breast cancer pathogenesis. Cancer Res. 69, 7459-7465 (2009).
87. Chen, J. M., Ferec, C. & Cooper, D. N. A systematic analysis of disease-associated variants in the 3' regulatory regions of human protein-coding genes I: general principles and overview. Hum. Genet. 120, 1-21 (2006).
88. Tchatchou, S. et al. A variant affecting a putative miRNA target site in estrogen receptor (ESR) 1 is associated with breast cancer risk in premenopausal women. Carcinogenesis 30, 59-64 (2009).
89. Adams, B. D., Furneaux, H. & White, B. A. The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-α (ERα) and represses ERα messenger RNA and protein expression in breast cancer cell lines. Mol. Endocrinol. 21, 1132-1147 (2007).
90. Mishra, P. J., Humeniuk, R., Longo-Sorbello, G. S., Banerjee, D. & Bertino, J. R. A miR-24 microRNA binding-site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance. Proc. Natl Acad. Sci. USA 104, 13513-13518 (2007).
91. Mishra, P. J. et al. MiR-24 tumor suppressor activity is regulated independent of p53 and through a target site polymorphism. PLoS ONE 4, e8445 (2009).
92. Wurdinger, T. & Costa, F. F. Molecular therapy in the microRNA era. Pharmacogenomics J. 7, 297-304 (2007).
93. Spitz, M. R., Wu, X. & Mills, G. Integrative epidemiology: from risk assessment to outcome prediction. J. Clin. Oncol. 23, 267-275 (2005).
94. Savas, S. & Liu, G. Genetic variations as cancer prognostic markers: review and update. Hum. Mutat. 30, 1369-1377 (2009).
95. Mandola, M. V. et al. A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS mRNA levels. Pharmacogenetics 14, 319-327 (2004).
96. Lu, J. W. et al. Polymorphism in the 3'-untranslated region of the thymidylate synthase gene and sensitivity of stomach cancer to fluoropyrimidine-based chemotherapy. J. Hum. Genet. 51, 155-160 (2006).
97. Murphy, G., Pfeiffer, R., Camargo, M. C. & Rabkin, C. S. Meta-analysis shows that prevalence of Epstein-Barr virus-positive gastric cancer differs based on sex and anatomic location. Gastroenterology 137, 824-833 (2009).
98. Lung, R. W. et al. Modulation of LMP2A expression by a newly identified Epstein-Barr virus-encoded microRNA miR-BART22. Neoplasia 11, 1174-1184 (2009).
99. Lytle, J. R., Yario, T. A. & Steitz, J. A. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5' UTR as in the 3' UTR. Proc. Natl Acad. Sci. USA 104, 9667-9672 (2007).
100. Ehrenreich, I. M. & Purugganan, M. D. Sequence variation of MicroRNAs and their binding sites in Arabidopsis. Plant Physiol. 146, 1974-1982 (2008).
101. Kloosterman, W. P., Wienholds, E., Ketting, R. F. & Plasterk, R. H. Substrate requirements for let-7 function in the developing zebrafish embryo. Nucleic Acids Res. 32, 6284-6291 (2004).
102. Sunkar, R. & Zhu, J. K. Novel and stress-regulated microRNAs and other small RNAs from Arabidopsis. Plant Cell 16, 2001-2019 (2004).
103. Jopling, C. L., Yi, M., Lancaster, A. M., Lemon, S. M. & Sarnow, P. Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 309, 1577-1581 (2005).
104. Tay, Y., Zhang, J., Thomson, A. M., Lim, B. & Rigoutsos, I. MicroRNAs to Nanog, Oct4 and Sox2 coding regions modulate embryonic stem cell differentiation. Nature 455, 1124-1128 (2008).
105. Andersson, M. K. et al. The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response. BMC Cell Biol. 9, 37 (2008).
106. Duursma, A. M., Kedde, M., Schrier, M., le Sage, C. & Agami, R. miR-148 targets human DNMT3b protein coding region. RNA 14, 872-877 (2008).
107. Forman, J. J., Legesse-Miller, A. & Coller, H. A. A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence. Proc. Natl Acad. Sci. USA 105, 14879-14884 (2008).
108. Brennecke, J., Stark, A., Russell, R. B. & Cohen, S. M. Principles of microRNA-target recognition. PLoS Biol. 3, e85 (2005).
109. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661-678 (2007).
110. Merritt, W. M. et al. Dicer, Drosha, and outcomes in patients with ovarian cancer. N. Engl. J. Med. 359, 2641-2650 (2008).
111. Horikawa, Y. et al. Single nucleotide polymorphisms of microRNA machinery genes modify the risk of renal cell carcinoma. Clin. Cancer Res. 14, 7956-7962 (2008).
112. Lund, E., Guttinger, S., Calado, A., Dahlberg, J. E. & Kutay, U. Nuclear export of microRNA precursors. Science 303, 95-98 (2004).
113. Chiosea, S. et al. Overexpression of Dicer in precursor lesions of lung adenocarcinoma. Cancer Res. 67, 2345-2350 (2007).
114. Chiosea, S. et al. Up-regulation of dicer, a component of the MicroRNA machinery, in prostate adenocarcinoma. Am. J. Pathol. 169, 1812-1820 (2006).
115. Kumar, M. S. et al. Dicer1 functions as a haploinsufficient tumor suppressor. Genes Dev. 23, 2700-2704 (2009).
116. Melo, S. A. et al. A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function. Nature Genet. 41, 365-370 (2009).
117. Wan, D. et al. Two variants of the human hepatocellular carcinoma-associated HCAP1 gene and their effect on the growth of the human liver cancer cell line Hep3B. Genes Chromosom. Cancer 39, 48-58 (2004).
118. Suzuki, H. I. et al. Modulation of microRNA processing by p53. Nature 460, 529-533 (2009).
119. Mechanic, L. E. et al. Polymorphisms in XPD and TP53 and mutation in human lung cancer. Carcinogenesis 26, 597-604 (2005).
120. Hollstein, M., Sidransky, D., Vogelstein, B. & Harris, C. C. p53 mutations in human cancers. Science 253, 49-53 (1991).
121. Whibley, C., Pharoah, P. D. & Hollstein, M. p53 polymorphisms: cancer implications. Nature Rev. Cancer 9, 95-107 (2009).
122. Morin, R. D. et al. Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells. Genome Res. 18, 610-621 (2008).
123. Ruby, J. G. et al. Large-scale sequencing reveals 21 U-RNAs and additional microRNAs and endogenous siRNAs in C. elegans. Cell 127, 1193-1207 (2006).
124. Landgraf, P. et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129, 1401-1414 (2007).
125. Kuchenbauer, F. et al. In-depth characterization of the microRNA transcriptome in a leukemia progression model. Genome Res. 18, 1787-1797 (2008).
126. Ebhardt, H. A. et al. Meta-analysis of small RNA-sequencing errors reveals ubiquitous post-transcriptional RNA modifications. Nucleic Acids Res. 37, 2461-2470 (2009).
127. Fu, H. et al. Identification of human fetal liver miRNAs by a novel method. FEBS Lett. 579, 3849-3854 (2005).
128. Reid, J. G. et al. Mouse let-7 miRNA populations exhibit RNA editing that is constrained in the 5'-seed/cleavage/anchor regions and stabilize predicted mmu-let-7a:mRNA duplexes. Genome Res. 18, 1571-1581 (2008).
129. Thomson, J. M. et al. Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev. 20, 2202-2207 (2006).
130. Chuang, J. C. & Jones, P. A. Epigenetics and microRNAs. Pediatr. Res. 61, 24R-29R (2007).
131. Lehmann, U. et al. Epigenetic inactivation of microRNA gene hsa-mir-9-1 in human breast cancer. J. Pathol. 214, 17-24 (2008).
132. Yanaihara, N. et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9, 189-198 (2006).
133. Brueckner, B. et al. The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function. Cancer Res. 67, 1419-1423 (2007).
134. Clark, T. A. et al. Discovery of tissue-specific exons using comprehensive human exon microarrays. Genome Biol. 8, R64 (2007).
135. Sandberg, R., Neilson, J. R., Sarma, A., Sharp, P. A. & Burge, C. B. Proliferating cells express mRNAs with shortened 3' untranslated regions and fewer microRNA target sites. Science 320, 1643-1647 (2008).
136. Makeyev, E. V., Zhang, J., Carrasco, M. A. & Maniatis, T. The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol. Cell 27, 435-448 (2007).
137. Mayr, C. & Bartel, D. P. Widespread shortening of 3'UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell 138, 673-684 (2009).
138. Passetti, F., Ferreira, C. G. & Costa, F. F. The impact of microRNAs and alternative splicing in pharmacogenomics. Pharmacogenomics J. 9, 1-13 (2009).
139. Ponder, B. A. Cancer genetics. Nature 411, 336-341 (2001).
140. Pharoah, P. D., Dunning, A. M., Ponder, B. A. & Easton, D. F. Association studies for finding cancer-susceptibility genetic variants. Nature Rev. Cancer 4, 850-860 (2004).
141. Pharoah, P. D. et al. Polygenic susceptibility to breast cancer and implications for prevention. Nature Genet. 31, 33-36 (2002).
142. Hwang, H. W., Wentzel, E. A. & Mendell, J. T. A hexanucleotide element directs microRNA nuclear import. Science 315, 97-100 (2007).
143. Valadi, H. et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature Cell Biol. 9, 654-659 (2007).
144. Gibbings, D. J., Ciaudo, C, Erhardt, M. & Voinnet, O. Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nature Cell Biol. 11, 1143-1149 (2009).
145. Berezikov, E. et al. Evolutionary flux of canonical microRNAs and mirtrons in Drosophila. Nature Genet. 42, 6-9 (2010).
146. Okamura, K., Chung, W. J. & Lai, E. C. The long and short of inverted repeat genes in animals: microRNAs, mirtrons and hairpin RNAs. Cell Cycle 7, 2840-2845 (2008).
147. Ruby, J. G., Jan, C. H. & Bartel, D. P. Intronic microRNA precursors that bypass Drosha processing. Nature 448, 83-86 (2007).
148. Brendle, A. et al. Polymorphisms in predicted microRNA-binding sites in integrin genes and breast cancer: ITGB4 as prognostic marker. Carcinogenesis 29, 1394-1399 (2008).
149. Chen, K. et al. Polymorphisms in microRNA targets: a gold mine for molecular epidemiology. Carcinogenesis 29, 1306-1311 (2008).
150. Lee, R. C., Feinbaum, R. L. & Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843-854 (1993).
151. 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 75, 855-862 (1993).
152. Berezikov, E. et al. Diversity of microRNAs in human and chimpanzee brain. Nature Genet. 38, 1375-1377 (2006).
153. Aravin, A. & Tuschl, T. Identification and characterization of small RNAs involved in RNA silencing. FEBS Lett. 579, 5830-5840 (2005).
154. Stark, M. S. et al. Characterization of the Melanoma miRNAome by Deep Sequencing. PLoS ONE 5, e9685 (2010).
155. Heo, I. et al. TUT4 in concert with Lin28 suppresses microRNA biogenesis through pre-microRNA uridylation. Cell 138, 696-708 (2009).
156. Li, J., Yang, Z., Yu, B., Liu, J. & Chen, X. Methylation protects miRNAs and siRNAs from a 3'-end uridylation activity in Arabidopsis. Curr. Biol. 15, 1501-1507 (2005).
157. Wu, H. et al. miRNA profiling of naive, effector and memory CD8 T cells. PLoS ONE 2, e1020 (2007).
158. Waidner, L. A. et al. MicroRNAs of Gallid and Meleagrid herpesviruses show generally conserved genomic locations and are virus-specific. Virology 388, 128-136 (2009).
159. Griffiths-Jones, S., Grocock, R. J., van Dongen, S., Bateman, A. & Enright, A. J. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 34, D140-D144 (2006).
160. O'Toole, A. S., Miller, S., Haines, N., Zink, M. C. & Serra, M. J. Comprehensive thermodynamic analysis of 3' double-nucleotide overhangs neighboring Watson-Crick terminal base pairs. Nucleic Acids Res. 34, 3338-3344 (2006).
161. Qi, P. et al. Association of a variant in MIR 196A2 with susceptibility to hepatocellular carcinoma in male Chinese patients with chronic hepatitis B virus infection. Hum. Immunol. 12 Mar 2010 (doi:10.1016/j.humimm.2010.02.017).
162. Dou, T. et al. A polymorphism of microRNA196a genome region was associated with decreased risk of glioma in Chinese population. J. Cancer Res. Clin. Oncol. 14 Mar 2010 (doi: 10.1007/s00432-010-0844-5).
163. Chen, S. et al. An insertion/deletion polymorphism in the 3' untranslated region of beta-transducin repeat-containing protein (betaTrCP) is associated with susceptibility for hepatocellular carcinoma in Chinese. Biochem. Biophys. Res. Commun. 391, 552-556 (2010).
164. Sun, J. et al. Sequence variants at 22q13 are associated with prostate cancer risk. Cancer Res. 69, 10-15 (2009).