Expression Specificity of Disease-Associated lncRNAs: Toward Personalized Medicine

  • Quan Nguyen
  • Piero CarninciEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 394)


Long noncoding RNAs (lncRNAs) perform diverse regulatory functions in transcription, translation‚ chromatin modification, and cellular organization. Misregulation of lncRNAs is found linked to various human diseases. Compared to protein-coding RNAs‚ lncRNAs are more specific to organs, tissues, cell types, developmental stages, and disease conditions‚ making them promising candidates as diagnostic and prognostic biomarkers and as gene therapy targets. The functional annotation of mammalian genome (FANTOM) consortium utilizes cap analysis of gene expression (CAGE) method to quantify genome-wide activities of promoters and enhancers of coding and noncoding RNAs across a large collection of human and mouse tissues‚ cell types‚ diseases, and time-courses. The project discovered widespread transcription of major lncRNA classes, including lncRNAs derived from enhancers‚ bidirectional promoters‚ antisense lncRNAs‚ and repetitive elements. Results from FANTOM project enable assessment of lncRNA expression specificity across tissue and disease conditions‚ based on differential promoter and enhancer usage. More than 85 % of disease-related SNPs are within noncoding regions and are strikingly overrepresented in enhancer and promoter regions, suggestive of the importance of lncRNA loci at these SNP harboring regions to human diseases. In this chapter‚ we discuss lncRNA expression specificity‚ review diverse functions of disease-associated lncRNAs‚ and present perspectives on their potential therapeutic applications for personalized medicine. The future development of lncRNA applications relies on technologies to identify and validate their functions‚ structures‚ and mechanisms. Comprehensive understanding of genome-wide interaction networks of lncRNAs with proteins, chromatins, and other RNAs in regulating cellular processes will allow personalized medicine to use lncRNAs as highly specific biomarkers in diagnosis‚ prognosis, and therapeutic targets.


Zinc Finger Nuclease lncRNA Expression lncRNA Locus Fantom Project Papillary Thyroid Carcinoma Susceptibility Candidate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Cap analysis of gene expression


Chromatin immunoprecipitation


Encyclopedia of DNA elements


Enhancer RNAs


Functional annotation of mammalian genome


Genome-wide association study


Long noncoding RNAs




Transcription start sites


RNA sequencing



We especially thank FANTOM consortium for generating unprecedented amount of data for promoter-centric analysis in thousands of samples. We apologize for not being able to mention all important, related work from colleagues. This work was supported by a research grant from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT) to the RIKEN Center for Life Science Technologies and the Human Frontier Science Program to P.C.


  1. Akalin A et al (2009) Transcriptional features of genomic regulatory blocks. Genome Biol 10(4):R38PubMedPubMedCentralCrossRefGoogle Scholar
  2. Andersson R et al (2014a) An atlas of active enhancers across human cell types and tissues. Nature 507(7493):455–461PubMedCrossRefGoogle Scholar
  3. Andersson R et al (2014b) Nuclear stability and transcriptional directionality separate functionally distinct RNA species. Nat Commun 5:5336PubMedCrossRefGoogle Scholar
  4. Arner E et al (2015) Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells. Science 347(6225):1010–1014PubMedPubMedCentralCrossRefGoogle Scholar
  5. Azzalin CM, Lingner J (2014) Telomere functions grounding on TERRA firma. Trends in Cell Biol 25(1):29–36Google Scholar
  6. Bassett AR et al (2014) Considerations when investigating lncRNA function in vivo. In: Weigel D (ed) vol 3Google Scholar
  7. Bernstein BE et al (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489(7414):57–74CrossRefGoogle Scholar
  8. Bertone P et al (2004) Global identification of human transcribed sequences with genome tiling arrays. Science 306(5705):2242–2246PubMedCrossRefGoogle Scholar
  9. Carninci P et al (2003) Targeting a complex transcriptome: the construction of the mouse full-length cDNA encyclopedia. Genome Res 13(6b):1273–1289PubMedPubMedCentralCrossRefGoogle Scholar
  10. Carninci P et al (2005) The transcriptional landscape of the mammalian genome. Science 309(5740):1559–1563PubMedCrossRefGoogle Scholar
  11. Carninci P et al (2006) Genome-wide analysis of mammalian promoter architecture and evolution. Nat Genet 38(6):626–635PubMedCrossRefGoogle Scholar
  12. Carrieri C et al (2012) Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature 491(7424):454–457PubMedCrossRefGoogle Scholar
  13. Chakraborty D et al (2012) Combined RNAi and localization for functionally dissecting long noncoding RNAs. Nat Methods 9(4):360–362PubMedCrossRefGoogle Scholar
  14. Cheetham SW et al (2013) Long noncoding RNAs and the genetics of cancer. Br J Cancer 108(12):2419–2425PubMedPubMedCentralCrossRefGoogle Scholar
  15. Chen G et al (2013) LncRNADisease: a database for long-non-coding RNA-associated diseases. Nucleic Acids Res 41(Database issue):D983–D986PubMedPubMedCentralCrossRefGoogle Scholar
  16. Chu C et al (2011) Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol Cell 44(4):667–678PubMedPubMedCentralCrossRefGoogle Scholar
  17. Clark MB et al (2012) Genome-wide analysis of long noncoding RNA stability. Genome Res 22(5):885–898PubMedPubMedCentralCrossRefGoogle Scholar
  18. Core LJ et al (2014) Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers. Nat Genet 46(12):1311–1320PubMedPubMedCentralCrossRefGoogle Scholar
  19. Cui H et al (2014) The human long noncoding RNA lnc-IL7R regulates the inflammatory response. Eur J Immunol 44(7):2085PubMedPubMedCentralCrossRefGoogle Scholar
  20. de Silanes IL et al (2014) Identification of TERRA locus unveils a telomere protection role through association to nearly all chromosomes. Nat Commun 5Google Scholar
  21. de Wit E, de Laat W (2012) A decade of 3C technologies: insights into nuclear organization. Genes Dev 26(1):11–24PubMedPubMedCentralCrossRefGoogle Scholar
  22. Deng Q et al (2014) Prognostic value of long non-coding RNA HOTAIR in various cancers. PLoS ONE 9(10):e110059PubMedPubMedCentralCrossRefGoogle Scholar
  23. Derrien T et al (2012) The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22(9):1775–1789PubMedPubMedCentralCrossRefGoogle Scholar
  24. Ding Y et al (2014) In vivo genome-wide profiling of RNA secondary structure reveals novel regulatory features. Nature 505(7485):696–700PubMedCrossRefGoogle Scholar
  25. Djebali S et al (2012) Landscape of transcription in human cells. Nature 489(7414):101–108PubMedPubMedCentralCrossRefGoogle Scholar
  26. Engreitz JM et al (2013) The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science 341(6147):1237973PubMedPubMedCentralCrossRefGoogle Scholar
  27. Engreitz JM et al (2014) RNA-RNA interactions enable specific targeting of noncoding RNAs to nascent pre-mRNAs and chromatin sites. Cell 159(1):188–199PubMedPubMedCentralCrossRefGoogle Scholar
  28. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (2014) Recommendations from the EGAPP Working Group: does PCA3 testing for the diagnosis and management of prostate cancer improve patient health outcomes? Genet Med 16(4):338–346Google Scholar
  29. Faghihi MA et al (2008) Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of β-secretase expression. Nature Med 14(7):723–730PubMedPubMedCentralCrossRefGoogle Scholar
  30. Fatemi RP, Velmeshev D, Faghihi MA (2014) De-repressing LncRNA-targeted genes to upregulate gene expression: focus on small molecule therapeutics. Mol Ther Nucleic Acids 3:e196PubMedPubMedCentralCrossRefGoogle Scholar
  31. Faulkner GJ et al (2009) The regulated retrotransposon transcriptome of mammalian cells. Nat Genet 41(5):563–571PubMedCrossRefGoogle Scholar
  32. Forrest AR et al (2014) A promoter-level mammalian expression atlas. Nature 507(7493):462–470PubMedCrossRefGoogle Scholar
  33. Fort A et al (2014) Deep transcriptome profiling of mammalian stem cells supports a regulatory role for retrotransposons in pluripotency maintenance. Nat Genet 46:558–566PubMedCrossRefGoogle Scholar
  34. Francia S et al (2012) Site-specific DICER and DROSHA RNA products control the DNA-damage response. Nature 488(7410):231–235PubMedPubMedCentralCrossRefGoogle Scholar
  35. Gaj T, Gersbach CA, Barbas CF 3rd (2013) ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol 31(7):397–405PubMedPubMedCentralCrossRefGoogle Scholar
  36. Ge X et al (2013) Overexpression of long noncoding RNA PCAT-1 is a novel biomarker of poor prognosis in patients with colorectal cancer. Med Oncol 30(2):588PubMedCrossRefGoogle Scholar
  37. Gofrit ON et al (2014) DNA based therapy with diphtheria toxin-A BC-819: a phase 2b marker lesion trial in patients with intermediate risk nonmuscle invasive bladder cancer. J Urol 191(6):1697–1702PubMedCrossRefGoogle Scholar
  38. Gong J et al (2014) lncRNASNP: a database of SNPs in lncRNAs and their potential functions in human and mouse. Nucleic Acids Res 43(Database issue):D181–186Google Scholar
  39. Gupta RA et al (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464(7291):1071–1076PubMedPubMedCentralCrossRefGoogle Scholar
  40. Gutschner T et al (2013) The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res 73(3):1180–1189PubMedPubMedCentralCrossRefGoogle Scholar
  41. Guttman M et al (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458(7235):223–227PubMedPubMedCentralCrossRefGoogle Scholar
  42. Haberle V et al (2014) Two independent transcription initiation codes overlap on vertebrate core promoters. Nature 507(7492):381–385PubMedPubMedCentralCrossRefGoogle Scholar
  43. Hafner M et al (2010) Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141(1):129–141PubMedPubMedCentralCrossRefGoogle Scholar
  44. Hall LL et al (2014) Stable C0T-1 repeat RNA is abundant and is associated with euchromatic interphase chromosomes. Cell 156(5):907–919PubMedPubMedCentralCrossRefGoogle Scholar
  45. Halley P et al (2014) Regulation of the apolipoprotein gene cluster by a long noncoding RNA. Cell Rep 6(1):222–230PubMedPubMedCentralCrossRefGoogle Scholar
  46. Han J et al (2014) Efficient in vivo deletion of a large imprinted lncRNA by CRISPR/Cas9. RNA Biol 11(7):829–835PubMedPubMedCentralCrossRefGoogle Scholar
  47. Hangauer MJ, Vaughn IW, McManus MT (2013) Pervasive transcription of the human genome produces thousands of previously unidentified long intergenic noncoding RNAs. PLoS Genet 9(6):e1003569PubMedPubMedCentralCrossRefGoogle Scholar
  48. Helwak A, Tollervey D (2014) Mapping the miRNA interactome by cross-linking ligation and sequencing of hybrids (CLASH). Nat Protocols 9(3):711–728PubMedCrossRefGoogle Scholar
  49. Hirose T et al (2014) NEAT1 long noncoding RNA regulates transcription via protein sequestration within subnuclear bodies. Mol Biol Cell 25(1):169–183PubMedPubMedCentralCrossRefGoogle Scholar
  50. Hyde SC et al (2008) CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression. Nat Biotechnol 26(5):549–551PubMedCrossRefGoogle Scholar
  51. Iyer MK et al (2015) The landscape of long noncoding RNAs in the human transcriptome. Nat Genet 47(3):199–208Google Scholar
  52. Jendrzejewski J et al (2012) The polymorphism rs944289 predisposes to papillary thyroid carcinoma through a large intergenic noncoding RNA gene of tumor suppressor type. Proc Natl Acad Sci USA 109(22):8646–8651PubMedPubMedCentralCrossRefGoogle Scholar
  53. Jiang Q et al (2014) LncRNA2Target: a database for differentially expressed genes after lncRNA knockdown or overexpression. Nucleic Acids Res 43(Database issue):D193–196Google Scholar
  54. Johnson R, Guigo R (2014) The RIDL hypothesis: transposable elements as functional domains of long noncoding RNAs. RNA 20(7):959–976PubMedPubMedCentralCrossRefGoogle Scholar
  55. Kanamori-Katayama M et al (2011) Unamplified cap analysis of gene expression on a single-molecule sequencer. Genome Res 21(7):1150–1159PubMedPubMedCentralCrossRefGoogle Scholar
  56. Katayama S et al (2005) Antisense transcription in the mammalian transcriptome. Science 309(5740):1564–1566PubMedCrossRefGoogle Scholar
  57. Kelley D, Rinn J (2012) Transposable elements reveal a stem cell-specific class of long noncoding RNAs. Genome Biol 13(11):R107PubMedPubMedCentralCrossRefGoogle Scholar
  58. Keskin H et al (2014) Transcript-RNA-templated DNA recombination and repair. Nature 515(7527):436–439PubMedCrossRefGoogle Scholar
  59. Kim H, Kim J-S (2014) A guide to genome engineering with programmable nucleases. Nat Rev Genet 15(5):321–334PubMedCrossRefGoogle Scholar
  60. Kim T et al (2014) Long-range interaction and correlation between MYC enhancer and oncogenic long noncoding RNA CARLo-5. Proc Natl Acad Sci USA 111(11):4173–4178PubMedPubMedCentralCrossRefGoogle Scholar
  61. Kunarso G et al (2010) Transposable elements have rewired the core regulatory network of human embryonic stem cells. Nat Genet 42(7):631–634PubMedCrossRefGoogle Scholar
  62. Lam MT et al (2013) Rev-Erbs repress macrophage gene expression by inhibiting enhancer-directed transcription. Nature 498(7455):511–515PubMedPubMedCentralCrossRefGoogle Scholar
  63. Latos PA et al (2012) Airn transcriptional overlap, but not its lncRNA products, induces imprinted Igf2r silencing. Science 338(6113):1469–1472PubMedCrossRefGoogle Scholar
  64. Lau C-C et al (2014) Viral-human chimeric transcript predisposes risk to liver cancer development and progression. Cancer Cell 25(3):335–349PubMedCrossRefGoogle Scholar
  65. Li L, Chang HY (2014) Physiological roles of long noncoding RNAs: insight from knockout mice. Trends Cell Biol 24(10):594–602PubMedPubMedCentralCrossRefGoogle Scholar
  66. Li Z et al (2014a) The long noncoding RNA THRIL regulates TNFalpha expression through its interaction with hnRNPL. Proc Natl Acad Sci USA 111(3):1002–1007PubMedPubMedCentralCrossRefGoogle Scholar
  67. Li H et al (2014b) Overexpression of lncRNA H19 enhances carcinogenesis and metastasis of gastric cancer. Oncotarget 5(8):2318–2329PubMedPubMedCentralCrossRefGoogle Scholar
  68. Liu Y et al (2002) The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson’s disease susceptibility. Cell 111(2):209–218PubMedCrossRefGoogle Scholar
  69. Mao YS et al (2011) Direct visualization of the co-transcriptional assembly of a nuclear body by noncoding RNAs. Nat Cell Biol 13(1):95–101PubMedPubMedCentralCrossRefGoogle Scholar
  70. Marin-Bejar O et al (2013) Pint lincRNA connects the p53 pathway with epigenetic silencing by the polycomb repressive complex 2. Genome Biol 14(9):R104PubMedPubMedCentralCrossRefGoogle Scholar
  71. Meng L et al (2014) Towards a therapy for Angelman syndrome by targeting a long non-coding RNA. Nature 518(7539):409–412Google Scholar
  72. Mercer TR, Mattick JS (2013) Structure and function of long noncoding RNAs in epigenetic regulation. Nat Struct Mol Biol 20(3):300–307PubMedCrossRefGoogle Scholar
  73. Mercer TR et al (2008) Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci USA 105(2):716–721PubMedPubMedCentralCrossRefGoogle Scholar
  74. Modarresi F et al (2012) Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation. Nat Biotechnol 30(5):453–459PubMedPubMedCentralCrossRefGoogle Scholar
  75. Morris KV, Mattick JS (2014) The rise of regulatory RNA. Nat Rev Genet 15(6):423–437PubMedPubMedCentralCrossRefGoogle Scholar
  76. Mortimer SA, Kidwell MA, Doudna JA (2014) Insights into RNA structure and function from genome-wide studies. Nat Rev Genet 15:469PubMedCrossRefGoogle Scholar
  77. Mousavi K et al (2013) eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci. Mol Cell 51(5):606–617PubMedPubMedCentralCrossRefGoogle Scholar
  78. Necsulea A et al (2014) The evolution of lncRNA repertoires and expression patterns in tetrapods. Nature 505(7485):635–640PubMedCrossRefGoogle Scholar
  79. Overington JP, Al-Lazikani B, Hopkins AL (2006) How many drug targets are there? Nat Rev Drug Discov 5(12):993–996PubMedCrossRefGoogle Scholar
  80. Park C et al (2014) lncRNAtor: a comprehensive resource for functional investigation of long non-coding RNAs. Bioinformatics 30(17):2480–2485Google Scholar
  81. Pennisi E (2014) Lengthy RNAs earn respect as cellular players. Science 344(6188):1072PubMedCrossRefGoogle Scholar
  82. Porro A et al (2014) Functional characterization of the TERRA transcriptome at damaged telomeres. Nat Commun 5Google Scholar
  83. Prensner JR et al (2014) PCAT-1, a long noncoding RNA, regulates BRCA2 and controls homologous recombination in cancer. Cancer Res 74(6):1651–1660PubMedPubMedCentralCrossRefGoogle Scholar
  84. Pringle IA et al (2012) Rapid identification of novel functional promoters for gene therapy. J Mol Med (Berl) 90(12):1487–1496CrossRefGoogle Scholar
  85. Quek XC et al (2014) lncRNAdb v2.0: expanding the reference database for functional long noncoding RNAs. Nucleic Acids Res 43(Database issue):D168–173Google Scholar
  86. Quinn JJ et al (2014) Revealing long noncoding RNA architecture and functions using domain-specific chromatin isolation by RNA purification. Nat Biotechnol 32(9):933–940PubMedPubMedCentralCrossRefGoogle Scholar
  87. Rinn JL, Chang HY (2012) Genome regulation by long noncoding RNAs. Annu Rev Biochem 81:145–166PubMedCrossRefGoogle Scholar
  88. Rinn J, Guttman M (2014) RNA and dynamic nuclear organization. Science 345(6202):1240–1241PubMedPubMedCentralCrossRefGoogle Scholar
  89. Russ AP, Lampel S (2005) The druggable genome: an update. Drug Discovery Today 10(23–24):1607–1610PubMedCrossRefGoogle Scholar
  90. Schug J et al (2005) Promoter features related to tissue specificity as measured by Shannon entropy. Genome Biol 6(4):R33PubMedPubMedCentralCrossRefGoogle Scholar
  91. Severin J, Lizio M, Harshbarger J (2014) Interactive visualization and analysis of large-scale sequencing datasets using ZENBU. Nat Biotechnol 32(3):217–219Google Scholar
  92. Shukla R et al (2013) Endogenous retrotransposition activates oncogenic pathways in hepatocellular carcinoma. Cell 153(1):101–111PubMedPubMedCentralCrossRefGoogle Scholar
  93. Simon MD et al (2011) The genomic binding sites of a noncoding RNA. Proc Natl Acad Sci USA 108(51):20497–20502PubMedPubMedCentralCrossRefGoogle Scholar
  94. Stelzer Y et al (2014) The noncoding RNA IPW regulates the imprinted DLK1-DIO3 locus in an induced pluripotent stem cell model of Prader-Willi syndrome. Nat Genet 46(6):551–557PubMedCrossRefGoogle Scholar
  95. Sugimoto Y et al (2012) Analysis of CLIP and iCLIP methods for nucleotide-resolution studies of protein-RNA interactions. Genome Biol 13(8):R67PubMedPubMedCentralCrossRefGoogle Scholar
  96. Suzuki H et al (2009) The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line. Nat Genet 41(5):553–562PubMedCrossRefGoogle Scholar
  97. Takahashi H, Carninci P (2014) Widespread genome transcription: new possibilities for RNA therapies. Biochem Biophys Res Commun 452(2):294–301PubMedCrossRefGoogle Scholar
  98. Takahashi H et al (2012) 5’ end-centered expression profiling using cap-analysis gene expression and next-generation sequencing. Nat Protoc 7(3):542–561PubMedPubMedCentralCrossRefGoogle Scholar
  99. Thai P et al (2013) Characterization of a novel long noncoding RNA, SCAL1, induced by cigarette smoke and elevated in lung cancer cell lines. Am J Respir Cell Mol Biol 49(2):204–211PubMedPubMedCentralCrossRefGoogle Scholar
  100. Thorsen K et al (2011) Tumor-specific usage of alternative transcription start sites in colorectal cancer identified by genome-wide exon array analysis. BMC Genom 12(1):505CrossRefGoogle Scholar
  101. Trimarchi T et al (2014) Genome-wide mapping and characterization of notch-regulated long noncoding RNAs in acute leukemia. Cell 158(3):593–606PubMedPubMedCentralCrossRefGoogle Scholar
  102. Volders PJ et al (2015) An update on LNCipedia: a database for annotated human lncRNA sequences. Nucleic Acids Res 43(Database issue):D174–D180PubMedPubMedCentralCrossRefGoogle Scholar
  103. Walsh AL et al (2014) Long noncoding RNAs and prostate carcinogenesis: the missing ‘linc’? Trends Mol Med 20(8):428–436PubMedCrossRefGoogle Scholar
  104. Wan G et al (2013) A novel non-coding RNA lncRNA-JADE connects DNA damage signalling to histone H4 acetylation. EMBO J 32(21):2833–2847PubMedPubMedCentralCrossRefGoogle Scholar
  105. Wan Y et al (2014) Landscape and variation of RNA secondary structure across the human transcriptome. Nature 505(7485):706–709PubMedPubMedCentralCrossRefGoogle Scholar
  106. Wang J et al (2014) Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells. Nature 516:405–409Google Scholar
  107. Wang P et al (2014) The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science 344(6181):310–313PubMedCrossRefGoogle Scholar
  108. Ward LD, Kellis M (2012) Evidence of abundant purifying selection in humans for recently acquired regulatory functions. Science 337(6102):1675–1678PubMedPubMedCentralCrossRefGoogle Scholar
  109. Xiang JF et al (2014) Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus. Cell Res 24(5):513–531PubMedPubMedCentralCrossRefGoogle Scholar
  110. Xie C et al (2013) NONCODEv4: exploring the world of long non-coding RNA genes. Nucleic Acids Res 42(Database issue):D98–D103Google Scholar
  111. Yang F et al (2013) Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis. Mol Cell 49(6):1083–1096PubMedCrossRefGoogle Scholar
  112. Yildirim E et al (2013) Xist RNA is a potent suppressor of hematologic cancer in mice. Cell 152(4):727–742PubMedCrossRefGoogle Scholar
  113. Yu TY, Kao YW, Lin JJ (2014) Telomeric transcripts stimulate telomere recombination to suppress senescence in cells lacking telomerase. Proc Natl Acad Sci USA 111(9):3377–3382PubMedPubMedCentralCrossRefGoogle Scholar
  114. Yue F et al (2014) A comparative encyclopedia of DNA elements in the mouse genome. Nature 515(7527):355–364PubMedPubMedCentralCrossRefGoogle Scholar
  115. Zhang EB et al (2014a) Long noncoding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of miR-99a/miR-449a. Oncotarget 5(8):2276–2292PubMedPubMedCentralCrossRefGoogle Scholar
  116. Zhang EB et al (2014b) P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression. Cell Death Dis 5:e1243PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Division of Genomic Technologies, RIKEN Yokohama CampusRIKEN Center for Life Science TechnologiesYokohama CityJapan

Personalised recommendations