Long Noncoding RNAs in Lung Cancer

  • Anna Roth
  • Sven DiederichsEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 394)


Despite great progress in research and treatment options, lung cancer remains the leading cause of cancer-related deaths worldwide. Oncogenic driver mutations in protein-encoding genes were defined and allow for personalized therapies based on genetic diagnoses. Nonetheless, diagnosis of lung cancer mostly occurs at late stages, and chronic treatment is followed by a fast onset of chemoresistance. Hence, there is an urgent need for reliable biomarkers and alternative treatment options. With the era of whole genome and transcriptome sequencing technologies, long noncoding RNAs emerged as a novel class of versatile, functional RNA molecules. Although for most of them the mechanism of action remains to be defined, accumulating evidence confirms their involvement in various aspects of lung tumorigenesis. They are functional on the epigenetic, transcriptional, and posttranscriptional level and are regulators of pathophysiological key pathways including cell growth, apoptosis, and metastasis. Long noncoding RNAs are gaining increasing attention as potential biomarkers and a novel class of druggable molecules. It has become clear that we are only beginning to understand the complexity of tumorigenic processes. The clinical integration of long noncoding RNAs in terms of prognostic and predictive biomarker signatures and additional cancer targets could provide a chance to increase the therapeutic benefit. Here, we review the current knowledge about the expression, regulation, biological function, and clinical relevance of long noncoding RNAs in lung cancer.



We thank Lisa Langejürgen for help with literature search and contribution to selected lncRNA abstracts. Noncoding RNA research in the Diederichs lab is supported by the German Cancer Research Center (DKFZ), the Institute of Pathology at the University Hospital Heidelberg, the German Research Foundation (DFG: TRR77 TP B03, CellNetworks Excellence Cluster EcTop B5 and Di 1421/7-1), and the Helmholtz Society (VHI-CLL).


  1. Alaiyan B, Ilyayev N, Stojadinovic A, Izadjoo M, Roistacher M, Pavlov V, Tzivin V, Halle D, Pan H, Trink B, Gure AO, Nissan A (2013) Differential expression of colon cancer associated transcript1 (CCAT1) along the colonic adenoma-carcinoma sequence. BMC Cancer 13:196. doi: 10.1186/1471-2407-13-196 PubMedPubMedCentralCrossRefGoogle Scholar
  2. Alvarez ML, DiStefano JK (2011) Functional characterization of the plasmacytoma variant translocation 1 gene (PVT1) in diabetic nephropathy. PLoS ONE 6(4):e18671. doi: 10.1371/journal.pone.0018671 PubMedPubMedCentralCrossRefGoogle Scholar
  3. Amaral PP, Neyt C, Wilkins SJ, Askarian-Amiri ME, Sunkin SM, Perkins AC, Mattick JS (2009) Complex architecture and regulated expression of the SOX2OT locus during vertebrate development. RNA 15(11):2013–2027. doi: 10.1261/rna.1705309 PubMedPubMedCentralCrossRefGoogle Scholar
  4. Askarian-Amiri ME, Seyfoddin V, Smart CE, Wang J, Kim JE, Hansji H, Baguley BC, Finlay GJ, Leung EY (2014) Emerging role of long non-coding RNA SOX2OT in SOX2 regulation in breast cancer. PLoS ONE 9(7):e102140. doi: 10.1371/journal.pone.0102140 PubMedPubMedCentralCrossRefGoogle Scholar
  5. Balsara BR, Testa JR (2002) Chromosomal imbalances in human lung cancer. Oncogene 21(45):6877–6883. doi: 10.1038/sj.onc.1205836 PubMedCrossRefGoogle Scholar
  6. Barsotti AM, Beckerman R, Laptenko O, Huppi K, Caplen NJ, Prives C (2012) p53-Dependent induction of PVT1 and miR-1204. J Biol Chem 287(4):2509–2519. doi: 10.1074/jbc.M111.322875 PubMedPubMedCentralCrossRefGoogle Scholar
  7. Barsyte-Lovejoy D, Lau SK, Boutros PC, Khosravi F, Jurisica I, Andrulis IL, Tsao MS, Penn LZ (2006) The c-Myc oncogene directly induces the H19 noncoding RNA by allele-specific binding to potentiate tumorigenesis. Cancer Res 66(10):5330–5337. doi: 10.1158/0008-5472.CAN-06-0037 PubMedCrossRefGoogle Scholar
  8. Bartolomei MS, Zemel S, Tilghman SM (1991) Parental imprinting of the mouse H19 gene. Nature 351(6322):153–155. doi: 10.1038/351153a0 PubMedCrossRefGoogle Scholar
  9. Bass AJ, Watanabe H, Mermel CH, Yu S, Perner S, Verhaak RG, Kim SY, Wardwell L, Tamayo P, Gat-Viks I, Ramos AH, Woo MS, Weir BA, Getz G, Beroukhim R, O'Kelly M, Dutt A, Rozenblatt-Rosen O, Dziunycz P, Komisarof J, Chirieac LR, Lafargue CJ, Scheble V, Wilbertz T, Ma C, Rao S, Nakagawa H, Stairs DB, Lin L, Giordano TJ, Wagner P, Minna JD, Gazdar AF, Zhu CQ, Brose MS, Cecconello I, Jr UR, Marie SK, Dahl O, Shivdasani RA, Tsao MS, Rubin MA, Wong KK, Regev A, Hahn WC, Beer DG, Rustgi AK, Meyerson M (2009) SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nat Genet 41(11):1238–1242. doi: 10.1038/ng.465
  10. Batista PJ, Chang HY (2013) Long noncoding RNAs: cellular address codes in development and disease. Cell 152(6):1298–1307. doi: 10.1016/j.cell.2013.02.012 PubMedPubMedCentralCrossRefGoogle Scholar
  11. Becker K, Xu Y (2014) Management of tyrosine kinase inhibitor resistance in lung cancer with EGFR mutation. World J Clin Oncol 5(4):560–567. doi: 10.5306/wjco.v5.i4.560 PubMedPubMedCentralCrossRefGoogle Scholar
  12. Behrens C, Solis LM, Lin H, Yuan P, Tang X, Kadara H, Riquelme E, Galindo H, Moran CA, Kalhor N, Swisher SG, Simon GR, Stewart DJ, Lee JJ, Wistuba II (2013) EZH2 protein expression associates with the early pathogenesis, tumor progression, and prognosis of non-small cell lung carcinoma. Clin Cancer Res An Official J Am Assoc Cancer Res 19(23):6556–6565. doi: 10.1158/1078-0432.CCR-12-3946 CrossRefGoogle Scholar
  13. Benetatos L, Vartholomatos G, Hatzimichael E (2011) MEG3 imprinted gene contribution in tumorigenesis. Int J Cancer J International du Cancer 129(4):773–779. doi: 10.1002/ijc.26052 CrossRefGoogle Scholar
  14. Berteaux N, Lottin S, Monte D, Pinte S, Quatannens B, Coll J, Hondermarck H, Curgy JJ, Dugimont T, Adriaenssens E (2005) H19 mRNA-like noncoding RNA promotes breast cancer cell proliferation through positive control by E2F1. J Biol Chem 280(33):29625–29636. doi: 10.1074/jbc.M504033200 PubMedCrossRefGoogle Scholar
  15. Berteaux N, Aptel N, Cathala G, Genton C, Coll J, Daccache A, Spruyt N, Hondermarck H, Dugimont T, Curgy JJ, Forne T, Adriaenssens E (2008) A novel H19 antisense RNA overexpressed in breast cancer contributes to paternal IGF2 expression. Mol Cell Biol 28(22):6731–6745. doi: 10.1128/MCB.02103-07 PubMedPubMedCentralCrossRefGoogle Scholar
  16. Bertucci F, Lagarde A, Ferrari A, Finetti P, Charafe-Jauffret E, Van Laere S, Adelaide J, Viens P, Thomas G, Birnbaum D, Olschwang S (2012) 8q24 cancer risk allele associated with major metastatic risk in inflammatory breast cancer. PLoS ONE 7(5):e37943. doi: 10.1371/journal.pone.0037943 PubMedPubMedCentralCrossRefGoogle Scholar
  17. Boeri M, Pastorino U, Sozzi G (2012) Role of microRNAs in lung cancer: microRNA signatures in cancer prognosis. Cancer J 18(3):268–274. doi: 10.1097/PPO.0b013e318258b743 PubMedCrossRefGoogle Scholar
  18. Brunkow ME, Tilghman SM (1991) Ectopic expression of the H19 gene in mice causes prenatal lethality. Genes Dev 5(6):1092–1101PubMedCrossRefGoogle Scholar
  19. Byun HM, Wong HL, Birnstein EA, Wolff EM, Liang G, Yang AS (2007) Examination of IGF2 and H19 loss of imprinting in bladder cancer. Cancer Res 67(22):10753–10758. doi: 10.1158/0008-5472.CAN-07-0329 PubMedCrossRefGoogle Scholar
  20. Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A, Rinn JL (2011) Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev 25(18):1915–1927. doi: 10.1101/gad.17446611 PubMedPubMedCentralCrossRefGoogle Scholar
  21. Cai X, Cullen BR (2007) The imprinted H19 noncoding RNA is a primary microRNA precursor. RNA 13(3):313–316. doi: 10.1261/rna.351707
  22. Cancer Genome Atlas Research N (2012) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489(7417):519–525. doi: 10.1038/nature11404
  23. Cao S, Liu W, Li F, Zhao W, Qin C (2014) Decreased expression of lncRNA GAS5 predicts a poor prognosis in cervical cancer. Int J Clin Exp Pathol 7(10):6776–6783PubMedPubMedCentralGoogle Scholar
  24. Caporaso N, Gu F, Chatterjee N, Sheng-Chih J, Yu K, Yeager M, Chen C, Jacobs K, Wheeler W, Landi MT, Ziegler RG, Hunter DJ, Chanock S, Hankinson S, Kraft P, Bergen AW (2009) Genome-wide and candidate gene association study of cigarette smoking behaviors. PLoS ONE 4(2):e4653. doi: 10.1371/journal.pone.0004653 PubMedPubMedCentralCrossRefGoogle Scholar
  25. Carramusa L, Contino F, Ferro A, Minafra L, Perconti G, Giallongo A, Feo S (2007) The PVT-1 oncogene is a Myc protein target that is overexpressed in transformed cells. J Cell Physiol 213(2):511–518. doi: 10.1002/jcp.21133 PubMedCrossRefGoogle Scholar
  26. Cheetham SW, Gruhl F, Mattick JS, Dinger ME (2013) Long noncoding RNAs and the genetics of cancer. Br J Cancer 108(12):2419–2425. doi: 10.1038/bjc.2013.233 PubMedPubMedCentralCrossRefGoogle Scholar
  27. Chen W, Bocker W, Brosius J, Tiedge H (1997) Expression of neural BC200 RNA in human tumours. J Pathol 183(3):345–351. doi: 10.1002/(SICI)1096-9896(199711)183:3<345:AID-PATH930>3.0.CO;2-8 PubMedCrossRefGoogle Scholar
  28. Chen CL, Ip SM, Cheng D, Wong LC, Ngan HY (2000) Loss of imprinting of the IGF-II and H19 genes in epithelial ovarian cancer. Clin Cancer Res Official J Am Assoc Cancer Res 6(2):474–479Google Scholar
  29. Chen Y, Zhu X, Zhang X, Liu B, Huang L (2010) Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy. Mol Ther J Am Soc Gene Ther 18(9):1650–1656. doi: 10.1038/mt.2010.136 CrossRefGoogle Scholar
  30. Chen B, Yu M, Chang Q, Lu Y, Thakur C, Ma D, Yi Z, Chen F (2013) Mdig de-represses H19 large intergenic non-coding RNA (lincRNA) by down-regulating H3K9me3 and heterochromatin. Oncotarget 4(9):1427–1437PubMedPubMedCentralCrossRefGoogle Scholar
  31. Chen D, Zhang Z, Mao C, Zhou Y, Yu L, Yin Y, Wu S, Mou X, Zhu Y (2014a) ANRIL inhibits p15(INK4b) through the TGFbeta1 signaling pathway in human esophageal squamous cell carcinoma. Cell Immunol 289(1–2):91–96. doi: 10.1016/j.cellimm.2014.03.015 PubMedGoogle Scholar
  32. Chen HH, Almontashiri NA, Antoine D, Stewart AF (2014b) Functional genomics of the 9p21.3 locus for atherosclerosis: clarity or confusion? Curr Cardiol Rep 16(7):502. doi: 10.1007/s11886-014-0502-7 PubMedCrossRefGoogle Scholar
  33. Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong KK (2014c) Non-small-cell lung cancers: a heterogeneous set of diseases. Nat Rev Cancer 14(8):535–546. doi: 10.1038/nrc3775 PubMedCrossRefGoogle Scholar
  34. Cheng CJ, Bahal R, Babar IA, Pincus Z, Barrera F, Liu C, Svoronos A, Braddock DT, Glazer PM, Engelman DM, Saltzman WM, Slack FJ (2014a) MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature. doi: 10.1038/nature13905 Google Scholar
  35. Cheng N, Li X, Zhao C, Ren S, Chen X, Cai W, Zhao M, Zhang Y, Li J, Wang Q, Zhou C (2014b) Microarray expression profile of long non-coding RNAs in EGFR-TKIs resistance of human non-small cell lung cancer. Oncol Rep. doi: 10.3892/or.2014.3643 Google Scholar
  36. Chheang S, Brown K (2013) Lung cancer staging: clinical and radiologic perspectives. Semin Intervent Radiol 30(2):99–113. doi: 10.1055/s-0033-1342950 PubMedPubMedCentralCrossRefGoogle Scholar
  37. Chinen Y, Sakamoto N, Nagoshi H, Taki T, Maegawa S, Tatekawa S, Tsukamoto T, Mizutani S, Shimura Y, Yamamoto-Sugitani M, Kobayashi T, Matsumoto Y, Horiike S, Kuroda J, Taniwaki M (2014) 8q24 amplified segments involve novel fusion genes between NSMCE2 and long noncoding RNAs in acute myelogenous leukemia. J Hematol Oncol 7(1):68. doi: 10.1186/s13045-014-0068-2 PubMedPubMedCentralCrossRefGoogle Scholar
  38. Coccia EM, Cicala C, Charlesworth A, Ciccarelli C, Rossi GB, Philipson L, Sorrentino V (1992) Regulation and expression of a growth arrest-specific gene (gas5) during growth, differentiation, and development. Mol Cell Biol 12(8):3514–3521PubMedPubMedCentralCrossRefGoogle Scholar
  39. Cunnington MS, Santibanez Koref M, Mayosi BM, Burn J, Keavney B (2010) Chromosome 9p21 SNPs associated with multiple disease phenotypes correlate with ANRIL expression. PLoS Genet 6(4):e1000899. doi: 10.1371/journal.pgen.1000899 PubMedPubMedCentralCrossRefGoogle Scholar
  40. Davidson MR, Gazdar AF, Clarke BE (2013) The pivotal role of pathology in the management of lung cancer. J Thorac Dis 5(Suppl 5):S463–S478. doi: 10.3978/j.issn.2072-1439.2013.08.43 PubMedPubMedCentralGoogle Scholar
  41. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA (2002) Mutations of the BRAF gene in human cancer. Nature 417(6892):949–954. doi: 10.1038/nature00766 PubMedCrossRefGoogle Scholar
  42. DeChiara TM, Robertson EJ, Efstratiadis A (1991) Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64(4):849–859PubMedCrossRefGoogle Scholar
  43. Deng Q, Sun H, He B, Pan Y, Gao T, Chen J, Ying H, Liu X, Wang F, Xu Y, Wang S (2014) Prognostic value of long non-coding RNA HOTAIR in various cancers. PLoS ONE 9(10):e110059. doi: 10.1371/journal.pone.0110059 PubMedPubMedCentralCrossRefGoogle Scholar
  44. Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, Lagarde J, Veeravalli L, Ruan X, Ruan Y, Lassmann T, Carninci P, Brown JB, Lipovich L, Gonzalez JM, Thomas M, Davis CA, Shiekhattar R, Gingeras TR, Hubbard TJ, Notredame C, Harrow J, Guigo R (2012) The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22(9):1775–1789. doi: 10.1101/gr.132159.111 PubMedPubMedCentralCrossRefGoogle Scholar
  45. Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, Xue C, Marinov GK, Khatun J, Williams BA, Zaleski C, Rozowsky J, Roder M, Kokocinski F, Abdelhamid RF, Alioto T, Antoshechkin I, Baer MT, Bar NS, Batut P, Bell K, Bell I, Chakrabortty S, Chen X, Chrast J, Curado J, Derrien T, Drenkow J, Dumais E, Dumais J, Duttagupta R, Falconnet E, Fastuca M, Fejes-Toth K, Ferreira P, Foissac S, Fullwood MJ, Gao H, Gonzalez D, Gordon A, Gunawardena H, Howald C, Jha S, Johnson R, Kapranov P, King B, Kingswood C, Luo OJ, Park E, Persaud K, Preall JB, Ribeca P, Risk B, Robyr D, Sammeth M, Schaffer L, See LH, Shahab A, Skancke J, Suzuki AM, Takahashi H, Tilgner H, Trout D, Walters N, Wang H, Wrobel J, Yu Y, Ruan X, Hayashizaki Y, Harrow J, Gerstein M, Hubbard T, Reymond A, Antonarakis SE, Hannon G, Giddings MC, Ruan Y, Wold B, Carninci P, Guigo R, Gingeras TR (2012) Landscape of transcription in human cells. Nature 489(7414):101–108. doi: 10.1038/nature11233 PubMedPubMedCentralCrossRefGoogle Scholar
  46. Douc-Rasy S, Barrois M, Fogel S, Ahomadegbe JC, Stehelin D, Coll J, Riou G (1996) High incidence of loss of heterozygosity and abnormal imprinting of H19 and IGF2 genes in invasive cervical carcinomas. Uncoupling of H19 and IGF2 expression and biallelic hypomethylation of H19. Oncogene 12(2):423–430PubMedGoogle Scholar
  47. Eissmann M, Gutschner T, Hammerle M, Gunther S, Caudron-Herger M, Gross M, Schirmacher P, Rippe K, Braun T, Zornig M, Diederichs S (2012) Loss of the abundant nuclear non-coding RNA MALAT1 is compatible with life and development. RNA Biol 9(8):1076–1087. doi: 10.4161/rna.21089 PubMedPubMedCentralCrossRefGoogle Scholar
  48. Eissmann M, Schwamb B, Melzer IM, Moser J, Siele D, Kohl U, Rieker RJ, Wachter DL, Agaimy A, Herpel E, Baumgarten P, Mittelbronn M, Rakel S, Kogel D, Bohm S, Gutschner T, Diederichs S, Zornig M (2013) A functional yeast survival screen of tumor-derived cDNA libraries designed to identify anti-apoptotic mammalian oncogenes. PLoS ONE 8(5):e64873. doi: 10.1371/journal.pone.0064873 PubMedPubMedCentralCrossRefGoogle Scholar
  49. Elkin M, Ayesh S, Schneider T, de Groot N, Hochberg A, Ariel I (1998) The dynamics of the imprinted H19 gene expression in the mouse model of bladder carcinoma induced by N-butyl-N-(4-hydroxybutyl)nitrosamine. Carcinogenesis 19(12):2095–2099PubMedCrossRefGoogle Scholar
  50. El-Naggar AK, Lai S, Tucker SA, Clayman GL, Goepfert H, Hong WK, Huff V (1999) Frequent loss of imprinting at the IGF2 and H19 genes in head and neck squamous carcinoma. Oncogene 18(50):7063–7069. doi: 10.1038/sj.onc.1203192
  51. ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489(7414):57–74. doi: 10.1038/nature11247 CrossRefGoogle Scholar
  52. Erikson J, Nishikura K, Ar-Rushdi A, Finan J, Emanuel B, Lenoir G, Nowell PC, Croce CM (1983) Translocation of an immunoglobulin kappa locus to a region 3’ of an unrearranged c-myc oncogene enhances c-myc transcription. Proc Natl Acad Sci U.S.A 80(24):7581–7585Google Scholar
  53. Esteller M (2011) Non-coding RNAs in human disease. Nat Rev Genet 12(12):861–874. doi: 10.1038/nrg3074 PubMedCrossRefGoogle Scholar
  54. Fang Z, Wu L, Wang L, Yang Y, Meng Y, Yang H (2014) Increased expression of the long non-coding RNA UCA1 in tongue squamous cell carcinomas: a possible correlation with cancer metastasis. Oral Surg Oral Med Oral Pathol Oral Radiol 117(1):89–95. doi: 10.1016/j.oooo.2013.09.007 PubMedCrossRefGoogle Scholar
  55. Fantes J, Ragge NK, Lynch SA, McGill NI, Collin JR, Howard-Peebles PN, Hayward C, Vivian AJ, Williamson K, van Heyningen V, FitzPatrick DR (2003) Mutations in SOX2 cause anophthalmia. Nat Genet 33(4):461–463. doi: 10.1038/ng1120 PubMedCrossRefGoogle Scholar
  56. Feinberg AP (1996) Multiple genetic abnormalities of 11p15 in Wilms’ tumor. Med Pediatr Oncol 27(5):484–489. doi: 10.1002/(SICI)1096-911X(199611)27:5<484:AID-MPO16>3.0.CO;2-A PubMedCrossRefGoogle Scholar
  57. Flockhart RJ, Webster DE, Qu K, Mascarenhas N, Kovalski J, Kretz M, Khavari PA (2012) BRAFV600E remodels the melanocyte transcriptome and induces BANCR to regulate melanoma cell migration. Genome Res 22(6):1006–1014. doi: 10.1101/gr.140061.112 PubMedPubMedCentralCrossRefGoogle Scholar
  58. Folkersen L, Kyriakou T, Goel A, Peden J, Malarstig A, Paulsson-Berne G, Hamsten A, Hugh W, Franco-Cereceda A, Gabrielsen A, Eriksson P (2009) Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. Identification of eight new ANRIL splice variants. PLoS ONE 4(11):e7677. doi: 10.1371/journal.pone.0007677 PubMedPubMedCentralCrossRefGoogle Scholar
  59. Gabory A, Jammes H, Dandolo L (2010) The H19 locus: role of an imprinted non-coding RNA in growth and development. BioEssays: News Rev Mol Cell Dev Biol 32(6):473–480. doi: 10.1002/bies.200900170 CrossRefGoogle Scholar
  60. Gejman R, Batista DL, Zhong Y, Zhou Y, Zhang X, Swearingen B, Stratakis CA, Hedley-Whyte ET, Klibanski A (2008) Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 93(10):4119–4125. doi: 10.1210/jc.2007-2633 PubMedPubMedCentralCrossRefGoogle Scholar
  61. Ghoussaini M, Song H, Koessler T, Al Olama AA, Kote-Jarai Z, Driver KE, Pooley KA, Ramus SJ, Kjaer SK, Hogdall E, DiCioccio RA, Whittemore AS, Gayther SA, Giles GG, Guy M, Edwards SM, Morrison J, Donovan JL, Hamdy FC, Dearnaley DP, Ardern-Jones AT, Hall AL, O'Brien LT, Gehr-Swain BN, Wilkinson RA, Brown PM, Hopper JL, Neal DE, Pharoah PD, Ponder BA, Eeles RA, Easton DF, Dunning AM (2008) Multiple loci with different cancer specificities within the 8q24 gene desert. J Natl Cancer Inst 100(13):962–966. doi: 10.1093/jnci/djn190 PubMedPubMedCentralCrossRefGoogle Scholar
  62. Gordon FE, Nutt CL, Cheunsuchon P, Nakayama Y, Provencher KA, Rice KA, Zhou Y, Zhang X, Klibanski A (2010) Increased expression of angiogenic genes in the brains of mouse meg3-null embryos. Endocrinology 151(6):2443–2452. doi: 10.1210/en.2009-1151 PubMedPubMedCentralCrossRefGoogle Scholar
  63. Graveel CR, Jatkoe T, Madore SJ, Holt AL, Farnham PJ (2001) Expression profiling and identification of novel genes in hepatocellular carcinomas. Oncogene 20(21):2704–2712. doi: 10.1038/sj.onc.1204391 PubMedCrossRefGoogle Scholar
  64. Guan Y, Kuo WL, Stilwell JL, Takano H, Lapuk AV, Fridlyand J, Mao JH, Yu M, Miller MA, Santos JL, Kalloger SE, Carlson JW, Ginzinger DG, Celniker SE, Mills GB, Huntsman DG, Gray JW (2007) Amplification of PVT1 contributes to the pathophysiology of ovarian and breast cancer. Clin Cancer Res Official J Am Assoc Cancer Res 13(19):5745–5755. doi: 10.1158/1078-0432.CCR-06-2882 CrossRefGoogle Scholar
  65. Guo Q, Zhao Y, Chen J, Hu J, Wang S, Zhang D, Sun Y (2014) BRAF-activated long non-coding RNA contributes to colorectal cancer migration by inducing epithelial-mesenchymal transition. Oncol Lett 8(2):869–875. doi: 10.3892/ol.2014.2154 PubMedPubMedCentralGoogle Scholar
  66. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai MC, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464(7291):1071–1076. doi: 10.1038/nature08975 PubMedPubMedCentralCrossRefGoogle Scholar
  67. Gutschner T, Diederichs S (2012) The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol 9(6):703–719. doi: 10.4161/rna.20481 PubMedPubMedCentralCrossRefGoogle Scholar
  68. Gutschner T, Baas M, Diederichs S (2011) Noncoding RNA gene silencing through genomic integration of RNA destabilizing elements using zinc finger nucleases. Genome Res 21(11):1944–1954. doi: 10.1101/gr.122358.111 PubMedPubMedCentralCrossRefGoogle Scholar
  69. Gutschner T, Hammerle M, Diederichs S (2013a) MALAT1—a paradigm for long noncoding RNA function in cancer. J Mol Med 91(7):791–801. doi: 10.1007/s00109-013-1028-y
  70. Gutschner T, Hammerle M, Eissmann M, Hsu J, Kim Y, Hung G, Revenko A, Arun G, Stentrup M, Gross M, Zornig M, MacLeod AR, Spector DL, Diederichs S (2013b) The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res 73(3):1180–1189. doi: 10.1158/0008-5472.can-12-2850 PubMedPubMedCentralCrossRefGoogle Scholar
  71. Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458(7235):223–227. doi: 10.1038/nature07672 PubMedPubMedCentralCrossRefGoogle Scholar
  72. Haiman CA, Le Marchand L, Yamamato J, Stram DO, Sheng X, Kolonel LN, Wu AH, Reich D, Henderson BE (2007) A common genetic risk factor for colorectal and prostate cancer. Nat Genet 39(8):954–956. doi: 10.1038/ng2098 PubMedPubMedCentralCrossRefGoogle Scholar
  73. Han L, Kong R, Yin DD, Zhang EB, Xu TP, De W, Shu YQ (2013a) Low expression of long noncoding RNA GAS6-AS1 predicts a poor prognosis in patients with NSCLC. Med Oncol 30(4):694. doi: 10.1007/s12032-013-0694-5
  74. Han Y, Liu Y, Gui Y, Cai Z (2013b) Long intergenic non-coding RNA TUG1 is overexpressed in urothelial carcinoma of the bladder. J Surg Oncol 107(5):555–559. doi: 10.1002/jso.23264 PubMedCrossRefGoogle Scholar
  75. Han Y, Yang YN, Yuan HH, Zhang TT, Sui H, Wei XL, Liu L, Huang P, Zhang WJ, Bai YX (2014) UCA1, a long non-coding RNA up-regulated in colorectal cancer influences cell proliferation, apoptosis and cell cycle distribution. Pathology 46(5):396–401. doi: 10.1097/PAT.0000000000000125 PubMedCrossRefGoogle Scholar
  76. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. doi: 10.1016/j.cell.2011.02.013 PubMedCrossRefGoogle Scholar
  77. 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):e1003569. doi: 10.1371/journal.pgen.1003569 PubMedPubMedCentralCrossRefGoogle Scholar
  78. Hannon GJ, Beach D (1994) p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature 371(6494):257–261. doi: 10.1038/371257a0 PubMedCrossRefGoogle Scholar
  79. Hannus M, Beitzinger M, Engelmann JC, Weickert MT, Spang R, Hannus S, Meister G (2014) siPools: highly complex but accurately defined siRNA pools eliminate off-target effects. Nucleic Acids Res 42(12):8049–8061. doi: 10.1093/nar/gku480 PubMedPubMedCentralCrossRefGoogle Scholar
  80. Hanson RL, Craig DW, Millis MP, Yeatts KA, Kobes S, Pearson JV, Lee AM, Knowler WC, Nelson RG, Wolford JK (2007) Identification of PVT1 as a candidate gene for end-stage renal disease in type 2 diabetes using a pooling-based genome-wide single nucleotide polymorphism association study. Diabetes 56(4):975–983. doi: 10.2337/db06-1072 PubMedCrossRefGoogle Scholar
  81. Hao Y, Crenshaw T, Moulton T, Newcomb E, Tycko B (1993) Tumour-suppressor activity of H19 RNA. Nature 365(6448):764–767. doi: 10.1038/365764a0 PubMedCrossRefGoogle Scholar
  82. Hart JR, Roberts TC, Weinberg MS, Morris KV, Vogt PK (2014) MYC regulates the non-coding transcriptome. Oncotarget 5(24):12543–12554PubMedPubMedCentralCrossRefGoogle Scholar
  83. He X, Bao W, Li X, Chen Z, Che Q, Wang H, Wan XP (2014a) The long non-coding RNA HOTAIR is upregulated in endometrial carcinoma and correlates with poor prognosis. Int J Mol Med 33(2):325–332. doi: 10.3892/ijmm.2013.1570 PubMedGoogle Scholar
  84. He X, Tan X, Wang X, Jin H, Liu L, Ma L, Yu H, Fan Z (2014b) C-Myc-activated long noncoding RNA CCAT1 promotes colon cancer cell proliferation and invasion. Tumour Biol: J Int Soc Oncodevelopmental Biol Med. doi: 10.1007/s13277-014-2526-4 Google Scholar
  85. Hibi K, Nakamura H, Hirai A, Fujikake Y, Kasai Y, Akiyama S, Ito K, Takagi H (1996) Loss of H19 imprinting in esophageal cancer. Cancer Res 56(3):480–482PubMedGoogle Scholar
  86. Hirose T, Steitz JA (2001) Position within the host intron is critical for efficient processing of box C/D snoRNAs in mammalian cells. Proc Natl Acad Sci USA 98(23):12914–12919. doi: 10.1073/pnas.231490998 PubMedPubMedCentralCrossRefGoogle Scholar
  87. Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-Andre V, Sigova AA, Hoke HA, Young RA (2013) Super-enhancers in the control of cell identity and disease. Cell 155(4):934–947. doi: 10.1016/j.cell.2013.09.053 PubMedCrossRefGoogle Scholar
  88. Holdt LM, Hoffmann S, Sass K, Langenberger D, Scholz M, Krohn K, Finstermeier K, Stahringer A, Wilfert W, Beutner F, Gielen S, Schuler G, Gabel G, Bergert H, Bechmann I, Stadler PF, Thiery J, Teupser D (2013) Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell functions through trans-regulation of gene networks. PLoS Genet 9(7):e1003588. doi: 10.1371/journal.pgen.1003588 PubMedPubMedCentralCrossRefGoogle Scholar
  89. Hou Z, Zhao W, Zhou J, Shen L, Zhan P, Xu C, Chang C, Bi H, Zou J, Yao X, Huang R, Yu L, Yan J (2014) A long noncoding RNA SOX2OT regulates lung cancer cell proliferation and is a prognostic indicator of poor survival. Int J Biochem Cell Biol 53:380–388. doi: 10.1016/j.biocel.2014.06.004 PubMedCrossRefGoogle Scholar
  90. Hu YC, Yang ZH, Zhong KJ, Niu LJ, Pan XJ, Wu DC, Sun XJ, Zhou PK, Zhu MX, Huo YY (2009) Alteration of transcriptional profile in human bronchial epithelial cells induced by cigarette smoke condensate. Toxicol Lett 190(1):23–31. doi: 10.1016/j.toxlet.2009.06.860 PubMedCrossRefGoogle Scholar
  91. Huang L, Liao LM, Liu AW, Wu JB, Cheng XL, Lin JX, Zheng M (2014) Overexpression of long noncoding RNA HOTAIR predicts a poor prognosis in patients with cervical cancer. Arch Gynecol Obstet 290(4):717–723. doi: 10.1007/s00404-014-3236-2 PubMedCrossRefGoogle Scholar
  92. Huppi K, Siwarski D, Skurla R, Klinman D, Mushinski JF (1990) Pvt-1 transcripts are found in normal tissues and are altered by reciprocal(6;15) translocations in mouse plasmacytomas. Proc Natl Acad Sci USA 87(18):6964–6968PubMedPubMedCentralCrossRefGoogle Scholar
  93. Huppi K, Volfovsky N, Runfola T, Jones TL, Mackiewicz M, Martin SE, Mushinski JF, Stephens R, Caplen NJ (2008) The identification of microRNAs in a genomically unstable region of human chromosome 8q24. Mol Cancer Res: MCR 6(2):212–221. doi: 10.1158/1541-7786.MCR-07-0105 PubMedCrossRefGoogle Scholar
  94. Huppi K, Pitt JJ, Wahlberg BM, Caplen NJ (2012) The 8q24 gene desert: an oasis of non-coding transcriptional activity. Front Genet 3:69. doi: 10.3389/fgene.2012.00069 PubMedPubMedCentralCrossRefGoogle Scholar
  95. Hussenet T, du Manoir S (2010) SOX2 in squamous cell carcinoma: amplifying a pleiotropic oncogene along carcinogenesis. Cell Cycle 9(8):1480–1486PubMedCrossRefGoogle Scholar
  96. Hussenet T, Dali S, Exinger J, Monga B, Jost B, Dembele D, Martinet N, Thibault C, Huelsken J, Brambilla E, du Manoir S (2010) SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas. PloS ONE 5(1):e8960. doi: 10.1371/journal.pone.0008960
  97. Iacoangeli A, Lin Y, Morley EJ, Muslimov IA, Bianchi R, Reilly J, Weedon J, Diallo R, Bocker W, Tiedge H (2004) BC200 RNA in invasive and preinvasive breast cancer. Carcinogenesis 25(11):2125–2133. doi: 10.1093/carcin/bgh228 PubMedCrossRefGoogle Scholar
  98. Isfort RJ, Cody DB, Kerckaert GA, Tycko B, LeBoeuf RA (1997) Role of the H19 gene in Syrian hamster embryo cell tumorigenicity. Mol Carcinog 20(2):189–193PubMedCrossRefGoogle Scholar
  99. Ishibashi M, Kogo R, Shibata K, Sawada G, Takahashi Y, Kurashige J, Akiyoshi S, Sasaki S, Iwaya T, Sudo T, Sugimachi K, Mimori K, Wakabayashi G, Mori M (2013) Clinical significance of the expression of long non-coding RNA HOTAIR in primary hepatocellular carcinoma. Oncol Rep 29(3):946–950. doi: 10.3892/or.2012.2219 PubMedGoogle Scholar
  100. Iwakawa R, Takenaka M, Kohno T, Shimada Y, Totoki Y, Shibata T, Tsuta K, Nishikawa R, Noguchi M, Sato-Otsubo A, Ogawa S, Yokota J (2013) Genome-wide identification of genes with amplification and/or fusion in small cell lung cancer. Genes Chromosom Cancer 52(9):802–816. doi: 10.1002/gcc.22076 PubMedPubMedCentralCrossRefGoogle Scholar
  101. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90. doi: 10.3322/caac.20107 PubMedCrossRefGoogle Scholar
  102. Ji P, Diederichs S, Wang W, Boing S, Metzger R, Schneider PM, Tidow N, Brandt B, Buerger H, Bulk E, Thomas M, Berdel WE, Serve H, Muller-Tidow C (2003) MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 22(39):8031–8041. doi: 10.1038/sj.onc.1206928 PubMedCrossRefGoogle Scholar
  103. Johnson AD, Hwang SJ, Voorman A, Morrison A, Peloso GM, Hsu YH, Thanassoulis G, Newton-Cheh C, Rogers IS, Hoffmann U, Freedman JE, Fox CS, Psaty BM, Boerwinkle E, Cupples LA, O'Donnell CJ (2013a) Resequencing and clinical associations of the 9p21.3 region: a comprehensive investigation in the Framingham heart study. Circulation 127(7):799–810. doi: 10.1161/CIRCULATIONAHA.112.111559
  104. Johnson BE, Kris MG, Berry LD, Kwiatkowski DJ, Iafrate AJ, Varella-Garcia M, Wistuba II, Franklin WA, Ladanyi M, Su P-F, Sequist LV, Khuri FR, Garon EB, Pao W, Rudin CM, Schiller JH, Haura EB, Giaccone G, Minna JD, Bunn PA (2013b) A multicenter effort to identify driver mutations and employ targeted therapy in patients with lung adenocarcinomas: the lung cancer mutation consortium (LCMC). J Clin Oncol (ASCO Annu Meet Abstr) 31(8019)Google Scholar
  105. Kagami M, O'Sullivan MJ, Green AJ, Watabe Y, Arisaka O, Masawa N, Matsuoka K, Fukami M, Matsubara K, Kato F, Ferguson-Smith AC, Ogata T (2010) The IG-DMR and the MEG3-DMR at human chromosome 14q32.2: hierarchical interaction and distinct functional properties as imprinting control centers. PLoS Genet 6(6):e1000992. doi: 10.1371/journal.pgen.1000992 PubMedPubMedCentralCrossRefGoogle Scholar
  106. Kaneko K, Ito Y, Ono Y, Tainaka T, Tsuchiya H, Shimoyama Y, Ando H (2011) Gene expression profiling reveals upregulated UCA1 and BMF in gallbladder epithelia of children with pancreaticobiliary maljunction. J Pediatr Gastroenterol Nutr 52(6):744–750. doi: 10.1097/MPG.0b013e318214bd30 PubMedCrossRefGoogle Scholar
  107. Kaplan R, Luettich K, Heguy A, Hackett NR, Harvey BG, Crystal RG (2003) Monoallelic up-regulation of the imprinted H19 gene in airway epithelium of phenotypically normal cigarette smokers. Cancer Res 63(7):1475–1482PubMedGoogle Scholar
  108. Kasinski AL, Kelnar K, Stahlhut C, Orellana E, Zhao J, Shimer E, Dysart S, Chen X, Bader AG, Slack FJ (2014) A combinatorial microRNA therapeutics approach to suppressing non-small cell lung cancer. Oncogene. doi: 10.1038/onc.2014.282 PubMedPubMedCentralGoogle Scholar
  109. Kelberman D, Rizzoti K, Avilion A, Bitner-Glindzicz M, Cianfarani S, Collins J, Chong WK, Kirk JM, Achermann JC, Ross R, Carmignac D, Lovell-Badge R, Robinson IC, Dattani MT (2006) Mutations within Sox2/SOX2 are associated with abnormalities in the hypothalamo-pituitary-gonadal axis in mice and humans. J Clin Investig 116(9):2442–2455. doi: 10.1172/JCI28658 PubMedPubMedCentralGoogle Scholar
  110. Khaitan D, Dinger ME, Mazar J, Crawford J, Smith MA, Mattick JS, Perera RJ (2011) The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion. Cancer Res 71(11):3852–3862. doi: 10.1158/0008-5472.CAN-10-4460 PubMedCrossRefGoogle Scholar
  111. Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, Regev A, Lander ES, Rinn JL (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci USA 106(28):11667–11672. doi: 10.1073/pnas.0904715106 PubMedPubMedCentralCrossRefGoogle Scholar
  112. Kim HT, Choi BH, Niikawa N, Lee TS, Chang SI (1998) Frequent loss of imprinting of the H19 and IGF-II genes in ovarian tumors. Am J Med Genet 80(4):391–395PubMedCrossRefGoogle Scholar
  113. Kim K, Jutooru I, Chadalapaka G, Johnson G, Frank J, Burghardt R, Kim S, Safe S (2013) HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene 32(13):1616–1625. doi: 10.1038/onc.2012.193 PubMedPubMedCentralCrossRefGoogle Scholar
  114. Kim HP, Cho GA, Han SW, Shin JY, Jeong EG, Song SH, Lee WC, Lee KH, Bang D, Seo JS, Kim JI, Kim TY (2014a) Novel fusion transcripts in human gastric cancer revealed by transcriptome analysis. Oncogene 33(47):5434–5441. doi: 10.1038/onc.2013.490 PubMedCrossRefGoogle Scholar
  115. Kim T, Cui R, Jeon YJ, Lee JH, Sim H, Park JK, Fadda P, Tili E, Nakanishi H, Huh MI, Kim SH, Cho JH, Sung BH, Peng Y, Lee TJ, Luo Z, Sun HL, Wei H, Alder H, Oh JS, Shim KS, Ko SB, Croce CM (2014b) Long-range interaction and correlation between MYC enhancer and oncogenic long noncoding RNA CARLo-5. Proc Natl Acad Sci USA 111(11):4173–4178. doi: 10.1073/pnas.1400350111 PubMedPubMedCentralCrossRefGoogle Scholar
  116. Kino T, Hurt DE, Ichijo T, Nader N, Chrousos GP (2010) Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Science signaling 3 (107):ra8. doi: 10.1126/scisignal.2000568
  117. Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, Tanaka F, Shibata K, Suzuki A, Komune S, Miyano S, Mori M (2011) Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res 71(20):6320–6326. doi: 10.1158/0008-5472.CAN-11-1021 PubMedCrossRefGoogle Scholar
  118. Kondo M, Suzuki H, Ueda R, Osada H, Takagi K, Takahashi T (1995) Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers. Oncogene 10(6):1193–1198PubMedGoogle Scholar
  119. Kondrashov AV, Kiefmann M, Ebnet K, Khanam T, Muddashetty RS, Brosius J (2005) Inhibitory effect of naked neural BC1 RNA or BC200 RNA on eukaryotic in vitro translation systems is reversed by poly(A)-binding protein (PABP). J Mol Biol 353(1):88–103. doi: 10.1016/j.jmb.2005.07.049 PubMedCrossRefGoogle Scholar
  120. Kotake Y, Nakagawa T, Kitagawa K, Suzuki S, Liu N, Kitagawa M, Xiong Y (2011) Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene. Oncogene 30(16):1956–1962. doi: 10.1038/onc.2010.568 PubMedPubMedCentralCrossRefGoogle Scholar
  121. Lai MC, Yang Z, Zhou L, Zhu QQ, Xie HY, Zhang F, Wu LM, Chen LM, Zheng SS (2012) Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation. Med Oncol 29(3):1810–1816. doi: 10.1007/s12032-011-0004-z
  122. Langer CJ, Besse B, Gualberto A, Brambilla E, Soria JC (2010) The evolving role of histology in the management of advanced non-small-cell lung cancer. J Clin Oncol: Official J Am Soc Clin Oncol 28(36):5311–5320. doi: 10.1200/JCO.2010.28.8126 CrossRefGoogle Scholar
  123. Lee JT, Bartolomei MS (2013) X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell 152(6):1308–1323. doi: 10.1016/j.cell.2013.02.016 PubMedCrossRefGoogle Scholar
  124. Leeksma OC, Van Achterberg TA, Tsumura Y, Toshima J, Eldering E, Kroes WG, Mellink C, Spaargaren M, Mizuno K, Pannekoek H, de Vries CJ (2002) Human sprouty 4, a new ras antagonist on 5q31, interacts with the dual specificity kinase TESK1. Eur J Biochem FEBS 269(10):2546–2556CrossRefGoogle Scholar
  125. Leighton PA, Ingram RS, Eggenschwiler J, Efstratiadis A, Tilghman SM (1995) Disruption of imprinting caused by deletion of the H19 gene region in mice. Nature 375(6526):34–39. doi: 10.1038/375034a0 PubMedCrossRefGoogle Scholar
  126. Li CH, Chen Y (2013) Targeting long non-coding RNAs in cancers: progress and prospects. Int J Biochem Cell Biol 45(8):1895–1910. doi: 10.1016/j.biocel.2013.05.030 PubMedCrossRefGoogle Scholar
  127. Li L, Liu B, Wapinski OL, Tsai MC, Qu K, Zhang J, Carlson JC, Lin M, Fang F, Gupta RA, Helms JA, Chang HY (2013) Targeted disruption of Hotair leads to homeotic transformation and gene derepression. Cell Rep 5(1):3–12. doi: 10.1016/j.celrep.2013.09.003 PubMedPubMedCentralCrossRefGoogle Scholar
  128. Li R, Zhang L, Jia L, Duan Y, Li Y, Bao L, Sha N (2014) Long non-coding RNA BANCR promotes proliferation in malignant melanoma by regulating MAPK pathway activation. PLoS ONE 9(6):e100893. doi: 10.1371/journal.pone.0100893 PubMedPubMedCentralCrossRefGoogle Scholar
  129. Liloglou T, Bediaga NG, Brown BR, Field JK, Davies MP (2014) Epigenetic biomarkers in lung cancer. Cancer Lett 342(2):200–212. doi: 10.1016/j.canlet.2012.04.018 PubMedCrossRefGoogle Scholar
  130. Lin SP, Youngson N, Takada S, Seitz H, Reik W, Paulsen M, Cavaille J, Ferguson-Smith AC (2003) Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlk1-Gtl2 imprinted cluster on mouse chromosome 12. Nat Genet 35(1):97–102. doi: 10.1038/ng1233 PubMedCrossRefGoogle Scholar
  131. Lin D, Pestova TV, Hellen CU, Tiedge H (2008) Translational control by a small RNA: dendritic BC1 RNA targets the eukaryotic initiation factor 4A helicase mechanism. Mol Cell Biol 28(9):3008–3019. doi: 10.1128/MCB.01800-07 PubMedPubMedCentralCrossRefGoogle Scholar
  132. Ling H, Fabbri M, Calin GA (2013a) MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov 12(11):847–865. doi: 10.1038/nrd4140 PubMedPubMedCentralCrossRefGoogle Scholar
  133. Ling H, Spizzo R, Atlasi Y, Nicoloso M, Shimizu M, Redis RS, Nishida N, Gafa R, Song J, Guo Z, Ivan C, Barbarotto E, De Vries I, Zhang X, Ferracin M, Churchman M, van Galen JF, Beverloo BH, Shariati M, Haderk F, Estecio MR, Garcia-Manero G, Patijn GA, Gotley DC, Bhardwaj V, Shureiqi I, Sen S, Multani AS, Welsh J, Yamamoto K, Taniguchi I, Song MA, Gallinger S, Casey G, Thibodeau SN, Le Marchand L, Tiirikainen M, Mani SA, Zhang W, Davuluri RV, Mimori K, Mori M, Sieuwerts AM, Martens JW, Tomlinson I, Negrini M, Berindan-Neagoe I, Foekens JA, Hamilton SR, Lanza G, Kopetz S, Fodde R, Calin GA (2013b) CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer. Genome Res 23(9):1446–1461. doi: 10.1101/gr.152942.112 PubMedPubMedCentralCrossRefGoogle Scholar
  134. Liu F, Killian JK, Yang M, Walker RL, Hong JA, Zhang M, Davis S, Zhang Y, Hussain M, Xi S, Rao M, Meltzer PA, Schrump DS (2010) Epigenomic alterations and gene expression profiles in respiratory epithelia exposed to cigarette smoke condensate. Oncogene 29(25):3650–3664. doi: 10.1038/onc.2010.129 PubMedCrossRefGoogle Scholar
  135. Liu SP, Yang JX, Cao DY, Shen K (2013a) Identification of differentially expressed long non-coding RNAs in human ovarian cancer cells with different metastatic potentials. Cancer Biol Med 10(3):138–141. doi: 10.7497/j.issn.2095-3941.2013.03.003 PubMedPubMedCentralGoogle Scholar
  136. Liu XH, Liu ZL, Sun M, Liu J, Wang ZX, De W (2013b) The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis in non-small cell lung cancer. BMC Cancer 13:464. doi: 10.1186/1471-2407-13-464 PubMedPubMedCentralCrossRefGoogle Scholar
  137. Liu Z, Sun M, Lu K, Liu J, Zhang M, Wu W, De W, Wang Z, Wang R (2013c) The long noncoding RNA HOTAIR contributes to cisplatin resistance of human lung adenocarcinoma cells via downregualtion of p21(WAF1/CIP1) expression. PLoS ONE 8(10):e77293. doi: 10.1371/journal.pone.0077293 PubMedPubMedCentralCrossRefGoogle Scholar
  138. Loewen G, Jayawickramarajah J, Zhuo Y, Shan B (2014) Functions of lncRNA HOTAIR in lung cancer. J Hematol Oncol 7(1):90. doi: 10.1186/s13045-014-0090-4 PubMedPubMedCentralCrossRefGoogle Scholar
  139. Lu Y, Chang Q, Zhang Y, Beezhold K, Rojanasakul Y, Zhao H, Castranova V, Shi X, Chen F (2009) Lung cancer-associated JmjC domain protein mdig suppresses formation of tri-methyl lysine 9 of histone H3. Cell Cycle 8(13):2101–2109PubMedCrossRefGoogle Scholar
  140. Lu KH, Li W, Liu XH, Sun M, Zhang ML, Wu WQ, Xie WP, Hou YY (2013) Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression. BMC Cancer 13:461. doi: 10.1186/1471-2407-13-461 PubMedPubMedCentralCrossRefGoogle Scholar
  141. Luo M, Li Z, Wang W, Zeng Y, Liu Z, Qiu J (2013) Long non-coding RNA H19 increases bladder cancer metastasis by associating with EZH2 and inhibiting E-cadherin expression. Cancer Lett 333(2):213–221. doi: 10.1016/j.canlet.2013.01.033 PubMedCrossRefGoogle Scholar
  142. Luo J, Tang L, Zhang J, Ni J, Zhang HP, Zhang L, Xu JF, Zheng D (2014) Long non-coding RNA CARLo-5 is a negative prognostic factor and exhibits tumor pro-oncogenic activity in non-small cell lung cancer. Tumour Biol: J Int Soc Oncodevelopmental Biol Med 35(11):11541–11549. doi: 10.1007/s13277-014-2442-7 CrossRefGoogle Scholar
  143. Lv XB, Lian GY, Wang HR, Song E, Yao H, Wang MH (2013) Long noncoding RNA HOTAIR is a prognostic marker for esophageal squamous cell carcinoma progression and survival. PLoS ONE 8(5):e63516. doi: 10.1371/journal.pone.0063516 PubMedPubMedCentralCrossRefGoogle Scholar
  144. Ma MZ, Kong X, Weng MZ, Zhang MD, Qin YY, Gong W, Zhang WJ, Quan ZW (2014) Long non-coding RNA-LET is a positive prognostic factor and exhibits tumor-suppressive activity in gallbladder cancer. Mol Carcinog. doi: 10.1002/mc.22215 Google Scholar
  145. Martignetti JA, Brosius J (1993) BC200 RNA: a neural RNA polymerase III product encoded by a monomeric Alu element. Proc Natl Acad Sci USA 90(24):11563–11567PubMedPubMedCentralCrossRefGoogle Scholar
  146. Matouk IJ, DeGroot N, Mezan S, Ayesh S, Abu-lail R, Hochberg A, Galun E (2007) The H19 non-coding RNA is essential for human tumor growth. PLoS ONE 2(9):e845. doi: 10.1371/journal.pone.0000845 PubMedPubMedCentralCrossRefGoogle Scholar
  147. Matouk IJ, Mezan S, Mizrahi A, Ohana P, Abu-Lail R, Fellig Y, Degroot N, Galun E, Hochberg A (2010) The oncofetal H19 RNA connection: hypoxia, p53 and cancer. Biochimica et biophysica acta 1803(4):443–451. doi: 10.1016/j.bbamcr.2010.01.010
  148. Matouk IJ, Raveh E, Abu-lail R, Mezan S, Gilon M, Gershtain E, Birman T, Gallula J, Schneider T, Barkali M, Richler C, Fellig Y, Sorin V, Hubert A, Hochberg A, Czerniak A (2014) Oncofetal H19 RNA promotes tumor metastasis. Biochimica et biophysica acta 1843(7):1414–1426. doi: 10.1016/j.bbamcr.2014.03.023
  149. Mercer TR, Dinger ME, Sunkin SM, Mehler MF, Mattick JS (2008) Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci USA 105(2):716–721. doi: 10.1073/pnas.0706729105 PubMedPubMedCentralCrossRefGoogle Scholar
  150. Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10(3):155–159. doi: 10.1038/nrg2521 PubMedCrossRefGoogle Scholar
  151. Mikkelsen TS, Ku M, Jaffe DB, Issac B, Lieberman E, Giannoukos G, Alvarez P, Brockman W, Kim TK, Koche RP, Lee W, Mendenhall E, O'Donovan A, Presser A, Russ C, Xie X, Meissner A, Wernig M, Jaenisch R, Nusbaum C, Lander ES, Bernstein BE (2007) Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448(7153):553–560. doi: 10.1038/nature06008 PubMedPubMedCentralCrossRefGoogle Scholar
  152. Millis MP, Bowen D, Kingsley C, Watanabe RM, Wolford JK (2007) Variants in the plasmacytoma variant translocation gene (PVT1) are associated with end-stage renal disease attributed to type 1 diabetes. Diabetes 56(12):3027–3032. doi: 10.2337/db07-0675 PubMedCrossRefGoogle Scholar
  153. Miyoshi N, Wagatsuma H, Wakana S, Shiroishi T, Nomura M, Aisaka K, Kohda T, Surani MA, Kaneko-Ishino T, Ishino F (2000) Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q. Genes Cells: Devoted Mol Cell Mech 5(3):211–220CrossRefGoogle Scholar
  154. Monroig PD, Chen L, Zhang S, Calin GA (2014) Small molecule compounds targeting miRNAs for cancer therapy. Adv Drug Deliv Rev. doi: 10.1016/j.addr.2014.09.002 Google Scholar
  155. Morton ML, Bai X, Merry CR, Linden PA, Khalil AM, Leidner RS, Thompson CL (2014) Identification of mRNAs and lincRNAs associated with lung cancer progression using next-generation RNA sequencing from laser micro-dissected archival FFPE tissue specimens. Lung Cancer 85(1):31–39. doi: 10.1016/j.lungcan.2014.03.020 PubMedPubMedCentralCrossRefGoogle Scholar
  156. Moulton T, Chung WY, Yuan L, Hensle T, Waber P, Nisen P, Tycko B (1996) Genomic imprinting and Wilms’ tumor. Med Pediatr Oncol 27(5):476–483. doi: 10.1002/(SICI)1096-911X(199611)27:5<476:AID-MPO15>3.0.CO;2-8 PubMedCrossRefGoogle Scholar
  157. Mourtada-Maarabouni M, Williams GT (2013) Growth arrest on inhibition of nonsense-mediated decay is mediated by noncoding RNA GAS5. BioMed Res Int 2013:358015. doi: 10.1155/2013/358015 PubMedPubMedCentralCrossRefGoogle Scholar
  158. Mourtada-Maarabouni M, Pickard MR, Hedge VL, Farzaneh F, Williams GT (2009) GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene 28(2):195–208. doi: 10.1038/onc.2008.373 PubMedCrossRefGoogle Scholar
  159. Nagoshi H, Taki T, Hanamura I, Nitta M, Otsuki T, Nishida K, Okuda K, Sakamoto N, Kobayashi S, Yamamoto-Sugitani M, Tsutsumi Y, Kobayashi T, Matsumoto Y, Horiike S, Kuroda J, Taniwaki M (2012) Frequent PVT1 rearrangement and novel chimeric genes PVT1-NBEA and PVT1-WWOX occur in multiple myeloma with 8q24 abnormality. Cancer Res 72(19):4954–4962. doi: 10.1158/0008-5472.CAN-12-0213 PubMedCrossRefGoogle Scholar
  160. Nakagawa S, Ip JY, Shioi G, Tripathi V, Zong X, Hirose T, Prasanth KV (2012) Malat1 is not an essential component of nuclear speckles in mice. RNA 18(8):1487–1499. doi: 10.1261/rna.033217.112
  161. Nakagawa T, Endo H, Yokoyama M, Abe J, Tamai K, Tanaka N, Sato I, Takahashi S, Kondo T, Satoh K (2013) Large noncoding RNA HOTAIR enhances aggressive biological behavior and is associated with short disease-free survival in human non-small cell lung cancer. Biochem Biophys Res Commun 436(2):319–324. doi: 10.1016/j.bbrc.2013.05.101 PubMedCrossRefGoogle Scholar
  162. Nguyen KS, Kobayashi S, Costa DB (2009) Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancers dependent on the epidermal growth factor receptor pathway. Clin Lung Cancer 10(4):281–289. doi: 10.3816/CLC.2009.n.039 PubMedPubMedCentralCrossRefGoogle Scholar
  163. Nie Y, Liu X, Qu S, Song E, Zou H, Gong C (2013) Long non-coding RNA HOTAIR is an independent prognostic marker for nasopharyngeal carcinoma progression and survival. Cancer Sci 104(4):458–464. doi: 10.1111/cas.12092 PubMedCrossRefGoogle Scholar
  164. Nie FQ, Sun M, Yang JS, Xie M, Xu TP, Xia R, Liu YW, Liu XH, Zhang EB, Lu KH, Su YQ (2014a) Long noncoding RNA ANRIL promotes non small cell lung cancer cells proliferation and inhibits apoptosis by silencing KLF2 and P21 expression. Mol Cancer Ther. doi: 10.1158/1535-7163.MCT-14-0492 PubMedGoogle Scholar
  165. Nie FQ, Zhu Q, Xu TP, Zou YF, Xie M, Sun M, Xia R, Lu KH (2014b) Long non-coding RNA MVIH indicates a poor prognosis for non-small cell lung cancer and promotes cell proliferation and invasion. Tumour Biol: J Int Soc Oncodevelopmental Biol Med 35(8):7587–7594. doi: 10.1007/s13277-014-2009-7 CrossRefGoogle Scholar
  166. Niinuma T, Suzuki H, Nojima M, Nosho K, Yamamoto H, Takamaru H, Yamamoto E, Maruyama R, Nobuoka T, Miyazaki Y, Nishida T, Bamba T, Kanda T, Ajioka Y, Taguchi T, Okahara S, Takahashi H, Nishida Y, Hosokawa M, Hasegawa T, Tokino T, Hirata K, Imai K, Toyota M, Shinomura Y (2012) Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. Cancer Res 72(5):1126–1136. doi: 10.1158/0008-5472.CAN-11-1803 PubMedCrossRefGoogle Scholar
  167. Nissan A, Stojadinovic A, Mitrani-Rosenbaum S, Halle D, Grinbaum R, Roistacher M, Bochem A, Dayanc BE, Ritter G, Gomceli I, Bostanci EB, Akoglu M, Chen YT, Old LJ, Gure AO (2012) Colon cancer associated transcript-1: a novel RNA expressed in malignant and pre-malignant human tissues. Int J Cancer J International du Cancer 130(7):1598–1606. doi: 10.1002/ijc.26170 CrossRefGoogle Scholar
  168. Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T, Stutz AM, Korshunov A, Reimand J, Schumacher SE, Beroukhim R, Ellison DW, Marshall CR, Lionel AC, Mack S, Dubuc A, Yao Y, Ramaswamy V, Luu B, Rolider A, Cavalli FM, Wang X, Remke M, Wu X, Chiu RY, Chu A, Chuah E, Corbett RD, Hoad GR, Jackman SD, Li Y, Lo A, Mungall KL, Nip KM, Qian JQ, Raymond AG, Thiessen NT, Varhol RJ, Birol I, Moore RA, Mungall AJ, Holt R, Kawauchi D, Roussel MF, Kool M, Jones DT, Witt H, Fernandez LA, Kenney AM, Wechsler-Reya RJ, Dirks P, Aviv T, Grajkowska WA, Perek-Polnik M, Haberler CC, Delattre O, Reynaud SS, Doz FF, Pernet-Fattet SS, Cho BK, Kim SK, Wang KC, Scheurlen W, Eberhart CG, Fevre-Montange M, Jouvet A, Pollack IF, Fan X, Muraszko KM, Gillespie GY, Di Rocco C, Massimi L, Michiels EM, Kloosterhof NK, French PJ, Kros JM, Olson JM, Ellenbogen RG, Zitterbart K, Kren L, Thompson RC, Cooper MK, Lach B, McLendon RE, Bigner DD, Fontebasso A, Albrecht S, Jabado N, Lindsey JC, Bailey S, Gupta N, Weiss WA, Bognar L, Klekner A, Van Meter TE, Kumabe T, Tominaga T, Elbabaa SK, Leonard JR, Rubin JB, Liau LM, Van Meir EG, Fouladi M, Nakamura H, Cinalli G, Garami M, Hauser P, Saad AG, Iolascon A, Jung S, Carlotti CG, Vibhakar R, Ra YS, Robinson S, Zollo M, Faria CC, Chan JA, Levy ML, Sorensen PH, Meyerson M, Pomeroy SL, Cho YJ, Bader GD, Tabori U, Hawkins CE, Bouffet E, Scherer SW, Rutka JT, Malkin D, Clifford SC, Jones SJ, Korbel JO, Pfister SM, Marra MA, Taylor MD (2012) Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature 488(7409):49–56. doi: 10.1038/nature11327 PubMedPubMedCentralCrossRefGoogle Scholar
  169. Ono H, Motoi N, Nagano H, Miyauchi E, Ushijima M, Matsuura M, Okumura S, Nishio M, Hirose T, Inase N, Ishikawa Y (2014) Long noncoding RNA HOTAIR is relevant to cellular proliferation, invasiveness, and clinical relapse in small-cell lung cancer. Cancer Med 3(3):632–642. doi: 10.1002/cam4.220 PubMedPubMedCentralCrossRefGoogle Scholar
  170. Onyango P, Feinberg AP (2011) A nucleolar protein, H19 opposite tumor suppressor (HOTS), is a tumor growth inhibitor encoded by a human imprinted H19 antisense transcript. Proc Natl Acad Sci USA 108(40):16759–16764. doi: 10.1073/pnas.1110904108 PubMedPubMedCentralCrossRefGoogle Scholar
  171. Pachnis V, Belayew A, Tilghman SM (1984) Locus unlinked to alpha-fetoprotein under the control of the murine raf and Rif genes. Proc Natl Acad Sci USA 81(17):5523–5527PubMedPubMedCentralCrossRefGoogle Scholar
  172. Padua Alves C, Fonseca AS, Muys BR, de Barros ELBR, Burger MC, de Souza JE, Valente V, Zago MA, Silva WA Jr (2013) Brief report: the lincRNA Hotair is required for epithelial-to-mesenchymal transition and stemness maintenance of cancer cell lines. Stem Cells 31(12):2827–2832. doi: 10.1002/stem.1547 PubMedCrossRefGoogle Scholar
  173. Pallis A, Briasoulis E, Linardou H, Papadimitriou C, Bafaloukos D, Kosmidis P, Murray S (2011) Mechanisms of resistance to epidermal growth factor receptor tyrosine kinase inhibitors in patients with advanced non-small-cell lung cancer: clinical and molecular considerations. Curr Med Chem 18(11):1613–1628PubMedCrossRefGoogle Scholar
  174. Pang KC, Frith MC, Mattick JS (2006) Rapid evolution of noncoding RNAs: lack of conservation does not mean lack of function. Trends Genet: TIG 22(1):1–5. doi: 10.1016/j.tig.2005.10.003 PubMedCrossRefGoogle Scholar
  175. Pang EJ, Yang R, Fu XB, Liu YF (2014) Overexpression of long non-coding RNA MALAT1 is correlated with clinical progression and unfavorable prognosis in pancreatic cancer. Tumour Biol: J Int Soc Oncodevelopmental Biol Med. doi: 10.1007/s13277-014-2850-8 Google Scholar
  176. Panzitt K, Tschernatsch MM, Guelly C, Moustafa T, Stradner M, Strohmaier HM, Buck CR, Denk H, Schroeder R, Trauner M, Zatloukal K (2007) Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology 132(1):330–342. doi: 10.1053/j.gastro.2006.08.026 PubMedCrossRefGoogle Scholar
  177. Pasmant E, Laurendeau I, Heron D, Vidaud M, Vidaud D, Bieche I (2007) Characterization of a germ-line deletion, including the entire INK4/ARF locus, in a melanoma-neural system tumor family: identification of ANRIL, an antisense noncoding RNA whose expression coclusters with ARF. Cancer Res 67(8):3963–3969. doi: 10.1158/0008-5472.CAN-06-2004 PubMedCrossRefGoogle Scholar
  178. Pasmant E, Sabbagh A, Vidaud M, Bieche I (2011) ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J: Official Publ Fed Am Soc Exp Biol 25(2):444–448. doi: 10.1096/fj.10-172452 CrossRefGoogle Scholar
  179. Pickard MR, Williams GT (2014) Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy. Breast Cancer Res Treat 145(2):359–370. doi: 10.1007/s10549-014-2974-y PubMedCrossRefGoogle Scholar
  180. Pillai RN, Ramalingam SS (2014) Advances in the diagnosis and treatment of non-small cell lung cancer. Mol Cancer Ther 13(3):557–564. doi: 10.1158/1535-7163.MCT-13-0669 PubMedCrossRefGoogle Scholar
  181. Pleasance ED, Stephens PJ, O'Meara S, McBride DJ, Meynert A, Jones D, Lin ML, Beare D, Lau KW, Greenman C, Varela I, Nik-Zainal S, Davies HR, Ordonez GR, Mudie LJ, Latimer C, Edkins S, Stebbings L, Chen L, Jia M, Leroy C, Marshall J, Menzies A, Butler A, Teague JW, Mangion J, Sun YA, McLaughlin SF, Peckham HE, Tsung EF, Costa GL, Lee CC, Minna JD, Gazdar A, Birney E, Rhodes MD, McKernan KJ, Stratton MR, Futreal PA, Campbell PJ (2010) A small-cell lung cancer genome with complex signatures of tobacco exposure. Nature 463(7278):184–190. doi: 10.1038/nature08629 PubMedPubMedCentralCrossRefGoogle Scholar
  182. Pomerantz MM, Ahmadiyeh N, Jia L, Herman P, Verzi MP, Doddapaneni H, Beckwith CA, Chan JA, Hills A, Davis M, Yao K, Kehoe SM, Lenz HJ, Haiman CA, Yan C, Henderson BE, Frenkel B, Barretina J, Bass A, Tabernero J, Baselga J, Regan MM, Manak JR, Shivdasani R, Coetzee GA, Freedman ML (2009) The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat Genet 41(8):882–884. doi: 10.1038/ng.403 PubMedPubMedCentralCrossRefGoogle Scholar
  183. Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136(4):629–641. doi: 10.1016/j.cell.2009.02.006 PubMedCrossRefGoogle Scholar
  184. Qiao HP, Gao WS, Huo JX, Yang ZS (2013) Long non-coding RNA GAS5 functions as a tumor suppressor in renal cell carcinoma. Asian Pac J Cancer Prev: APJCP 14(2):1077–1082PubMedCrossRefGoogle Scholar
  185. Qiu JJ, Lin YY, Ye LC, Ding JX, Feng WW, Jin HY, Zhang Y, Li Q, Hua KQ (2014a) Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer. Gynecol Oncol 134(1):121–128. doi: 10.1016/j.ygyno.2014.03.556 PubMedCrossRefGoogle Scholar
  186. Qiu M, Xu Y, Yang X, Wang J, Hu J, Xu L, Yin R (2014b) CCAT2 is a lung adenocarcinoma-specific long non-coding RNA and promotes invasion of non-small cell lung cancer. Tumour Biol: J Int Soc Oncodevelopmental Biol Med 35(6):5375–5380. doi: 10.1007/s13277-014-1700-z CrossRefGoogle Scholar
  187. Rachmilewitz J, Goshen R, Ariel I, Schneider T, de Groot N, Hochberg A (1992) Parental imprinting of the human H19 gene. FEBS Lett 309(1):25–28PubMedCrossRefGoogle Scholar
  188. Raho G, Barone V, Rossi D, Philipson L, Sorrentino V (2000) The gas 5 gene shows four alternative splicing patterns without coding for a protein. Gene 256(1–2):13–17PubMedCrossRefGoogle Scholar
  189. Redis RS, Sieuwerts AM, Look MP, Tudoran O, Ivan C, Spizzo R, Zhang X, de Weerd V, Shimizu M, Ling H, Buiga R, Pop V, Irimie A, Fodde R, Bedrosian I, Martens JW, Foekens JA, Berindan-Neagoe I, Calin GA (2013) CCAT2, a novel long non-coding RNA in breast cancer: expression study and clinical correlations. Oncotarget 4(10):1748–1762PubMedPubMedCentralCrossRefGoogle Scholar
  190. Reeve AE (1996) Role of genomic imprinting in Wilms’ tumour and overgrowth disorders. Med Pediatr Oncol 27(5):470–475. doi: 10.1002/(SICI)1096-911X(199611)27:5<470:AID-MPO14>3.0.CO;2-E PubMedCrossRefGoogle Scholar
  191. Reis EM, Verjovski-Almeida S (2012) Perspectives of long non-coding RNAs in cancer diagnostics. Front Genet 3:32. doi: 10.3389/fgene.2012.00032 PubMedPubMedCentralGoogle Scholar
  192. Ren XS, Yin MH, Zhang X, Wang Z, Feng SP, Wang GX, Luo YJ, Liang PZ, Yang XQ, He JX, Zhang BL (2014) Tumor-suppressive microRNA-449a induces growth arrest and senescence by targeting E2F3 in human lung cancer cells. Cancer Lett 344(2):195–203. doi: 10.1016/j.canlet.2013.10.031 PubMedCrossRefGoogle Scholar
  193. Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129(7):1311–1323. doi: 10.1016/j.cell.2007.05.022 PubMedPubMedCentralCrossRefGoogle Scholar
  194. Robson CN, Gnanapragasam V, Byrne RL, Collins AT, Neal DE (1999) Transforming growth factor-beta1 up-regulates p15, p21 and p27 and blocks cell cycling in G1 in human prostate epithelium. J Endocrinol 160(2):257–266PubMedCrossRefGoogle Scholar
  195. Sati S, Ghosh S, Jain V, Scaria V, Sengupta S (2012) Genome-wide analysis reveals distinct patterns of epigenetic features in long non-coding RNA loci. Nucleic Acids Res 40(20):10018–10031. doi: 10.1093/nar/gks776 PubMedPubMedCentralCrossRefGoogle Scholar
  196. Sayed D, Abdellatif M (2011) MicroRNAs in development and disease. Physiol Rev 91(3):827–887. doi: 10.1152/physrev.00006.2010 PubMedCrossRefGoogle Scholar
  197. Schmidt JV, Matteson PG, Jones BK, Guan XJ, Tilghman SM (2000) The Dlk1 and Gtl2 genes are linked and reciprocally imprinted. Genes Dev 14(16):1997–2002PubMedPubMedCentralGoogle Scholar
  198. Schmidt LH, Spieker T, Koschmieder S, Schaffers S, Humberg J, Jungen D, Bulk E, Hascher A, Wittmer D, Marra A, Hillejan L, Wiebe K, Berdel WE, Wiewrodt R, Muller-Tidow C (2011) The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth. J Thorac Oncol: Official Publ Int Assoc Study Lung Cancer 6(12):1984–1992. doi: 10.1097/JTO.0b013e3182307eac CrossRefGoogle Scholar
  199. Schneider C, King RM, Philipson L (1988) Genes specifically expressed at growth arrest of mammalian cells. Cell 54(6):787–793PubMedCrossRefGoogle Scholar
  200. Schorderet P, Duboule D (2011) Structural and functional differences in the long non-coding RNA hotair in mouse and human. PLoS Genet 7(5):e1002071. doi: 10.1371/journal.pgen.1002071 PubMedPubMedCentralCrossRefGoogle Scholar
  201. Schrock A, Bode M, Goke FJ, Bareiss PM, Schairer R, Wang H, Weichert W, Franzen A, Kirsten R, van Bremen T, Queisser A, Kristiansen G, Heasley L, Bootz F, Lengerke C, Perner S (2014) Expression and role of the embryonic protein SOX2 in head and neck squamous cell carcinoma. Carcinogenesis 35(7):1636–1642. doi: 10.1093/carcin/bgu094 PubMedCrossRefGoogle Scholar
  202. Schuster-Gossler K, Bilinski P, Sado T, Ferguson-Smith A, Gossler A (1998) The mouse Gtl2 gene is differentially expressed during embryonic development, encodes multiple alternatively spliced transcripts, and may act as an RNA. Dev Dyn Official Publ Am Assoc Anatomists 212(2):214–228. doi: 10.1002/(SICI)1097-0177(199806)212:2<214:AID-AJA6>3.0.CO;2-K Google Scholar
  203. Shahryari A, Rafiee MR, Fouani Y, Oliae NA, Samaei NM, Shafiee M, Semnani S, Vasei M, Mowla SJ (2014) Two novel splice variants of SOX2OT, SOX2OT-S1, and SOX2OT-S2 are coupregulated with SOX2 and OCT4 in esophageal squamous cell carcinoma. Stem Cells 32(1):126–134. doi: 10.1002/stem.1542 PubMedCrossRefGoogle Scholar
  204. Shen L, Chen L, Wang Y, Jiang X, Xia H, Zhuang Z (2014) Long noncoding RNA MALAT1 promotes brain metastasis by inducing epithelial-mesenchymal transition in lung cancer. J Neurooncol. doi: 10.1007/s11060-014-1613-0 Google Scholar
  205. Shi X, Sun M, Liu H, Yao Y, Kong R, Chen F, Song Y (2013a) A critical role for the long non-coding RNA GAS5 in proliferation and apoptosis in non-small-cell lung cancer. Mol Carcinog. doi: 10.1002/mc.22120 Google Scholar
  206. Shi X, Sun M, Liu H, Yao Y, Song Y (2013b) Long non-coding RNAs: a new frontier in the study of human diseases. Cancer Lett 339(2):159–166. doi: 10.1016/j.canlet.2013.06.013 PubMedCrossRefGoogle Scholar
  207. Shtivelman E, Bishop JM (1990) Effects of translocations on transcription from PVT. Mol Cell Biol 10(4):1835–1839PubMedPubMedCentralCrossRefGoogle Scholar
  208. Shtivelman E, Henglein B, Groitl P, Lipp M, Bishop JM (1989) Identification of a human transcription unit affected by the variant chromosomal translocations 2;8 and 8;22 of Burkitt lymphoma. Proc Natl Acad Sci USA 86(9):3257–3260PubMedPubMedCentralCrossRefGoogle Scholar
  209. Siegel R, Naishadham D, Jemal A (2013) Cancer statistics. CA Cancer J Clin 63(1):11–30. doi: 10.3322/caac.21166
  210. Silva JM, Perez DS, Pritchett JR, Halling ML, Tang H, Smith DI (2010) Identification of long stress-induced non-coding transcripts that have altered expression in cancer. Genomics 95(6):355–362. doi: 10.1016/j.ygeno.2010.02.009 PubMedCrossRefGoogle Scholar
  211. Sisodiya SM, Ragge NK, Cavalleri GL, Hever A, Lorenz B, Schneider A, Williamson KA, Stevens JM, Free SL, Thompson PJ, van Heyningen V, Fitzpatrick DR (2006) Role of SOX2 mutations in human hippocampal malformations and epilepsy. Epilepsia 47(3):534–542. doi: 10.1111/j.1528-1167.2006.00464.x PubMedCrossRefGoogle Scholar
  212. Smalheiser NR (2014) The RNA-centred view of the synapse: non-coding RNAs and synaptic plasticity. Philos Trans R Soc Lond Ser B, Biol Sci 369(1652). doi: 10.1098/rstb.2013.0504
  213. Smith CM, Steitz JA (1998) Classification of gas5 as a multi-small-nucleolar-RNA (snoRNA) host gene and a member of the 5’-terminal oligopyrimidine gene family reveals common features of snoRNA host genes. Mol Cell Biol 18(12):6897–6909PubMedPubMedCentralCrossRefGoogle Scholar
  214. Spiro SG, Silvestri GA (2005) One hundred years of lung cancer. Am J Respir Crit Care Med 172(5):523–529. doi: 10.1164/rccm.200504-531OE PubMedCrossRefGoogle Scholar
  215. Suda K, Mizuuchi H, Maehara Y, Mitsudomi T (2012) Acquired resistance mechanisms to tyrosine kinase inhibitors in lung cancer with activating epidermal growth factor receptor mutation–diversity, ductility, and destiny. Cancer Metastasis Rev 31(3–4):807–814. doi: 10.1007/s10555-012-9391-7 PubMedCrossRefGoogle Scholar
  216. Suemori H, Noguchi S (2000) Hox C cluster genes are dispensable for overall body plan of mouse embryonic development. Dev Biol 220(2):333–342. doi: 10.1006/dbio.2000.9651 PubMedCrossRefGoogle Scholar
  217. Sun M, Jin FY, Xia R, Kong R, Li JH, Xu TP, Liu YW, Zhang EB, Liu XH, De W (2014a) Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer. BMC Cancer 14:319. doi: 10.1186/1471-2407-14-319 PubMedPubMedCentralCrossRefGoogle Scholar
  218. Sun M, Liu XH, Lu KH, Nie FQ, Xia R, Kong R, Yang JS, Xu TP, Liu YW, Zou YF, Lu BB, Yin R, Zhang EB, Xu L, De W, Wang ZX (2014b) EZH2-mediated epigenetic suppression of long noncoding RNA SPRY4-IT1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial-mesenchymal transition. Cell Death Dis 5:e1298. doi: 10.1038/cddis.2014.256 PubMedPubMedCentralCrossRefGoogle Scholar
  219. Sun M, Liu XH, Wang KM, Nie FQ, Kong R, Yang JS, Xia R, Xu TP, Jin FY, Liu ZJ, Chen JF, Zhang EB, De W, Wang ZX (2014c) Downregulation of BRAF activated non-coding RNA is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelial-mesenchymal transition. Mol Cancer 13:68. doi: 10.1186/1476-4598-13-68 PubMedPubMedCentralCrossRefGoogle Scholar
  220. Sutcliffe JG, Milner RJ, Gottesfeld JM, Reynolds W (1984) Control of neuronal gene expression. Science 225(4668):1308–1315PubMedCrossRefGoogle Scholar
  221. Svoboda M, Slyskova J, Schneiderova M, Makovicky P, Bielik L, Levy M, Lipska L, Hemmelova B, Kala Z, Protivankova M, Vycital O, Liska V, Schwarzova L, Vodickova L, Vodicka P (2014) HOTAIR long non-coding RNA is a negative prognostic factor not only in primary tumors, but also in the blood of colorectal cancer patients. Carcinogenesis 35(7):1510–1515. doi: 10.1093/carcin/bgu055 PubMedCrossRefGoogle Scholar
  222. Taft RJ, Pheasant M, Mattick JS (2007) The relationship between non-protein-coding DNA and eukaryotic complexity. BioEssays: News Rev Mol Cell Dev Biol 29(3):288–299. doi: 10.1002/bies.20544 CrossRefGoogle Scholar
  223. Takahashi N, Okamoto A, Kobayashi R, Shirai M, Obata Y, Ogawa H, Sotomaru Y, Kono T (2009) Deletion of Gtl2, imprinted non-coding RNA, with its differentially methylated region induces lethal parent-origin-dependent defects in mice. Hum Mol Genet 18(10):1879–1888. doi: 10.1093/hmg/ddp108 PubMedCrossRefGoogle Scholar
  224. Takahashi Y, Sawada G, Kurashige J, Uchi R, Matsumura T, Ueo H, Takano Y, Eguchi H, Sudo T, Sugimachi K, Yamamoto H, Doki Y, Mori M, Mimori K (2014) Amplification of PVT-1 is involved in poor prognosis via apoptosis inhibition in colorectal cancers. Br J Cancer 110(1):164–171. doi: 10.1038/bjc.2013.698 PubMedPubMedCentralCrossRefGoogle Scholar
  225. Tano K, Mizuno R, Okada T, Rakwal R, Shibato J, Masuo Y, Ijiri K, Akimitsu N (2010) MALAT-1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility-related genes. FEBS Lett 584(22):4575–4580. doi: 10.1016/j.febslet.2010.10.008 PubMedCrossRefGoogle Scholar
  226. Tennis MA, Van Scoyk MM, Freeman SV, Vandervest KM, Nemenoff RA, Winn RA (2010) Sprouty-4 inhibits transformed cell growth, migration and invasion, and epithelial-mesenchymal transition, and is regulated by Wnt7A through PPARgamma in non-small cell lung cancer. Mol Cancer Res: MCR 8(6):833–843. doi: 10.1158/1541-7786.MCR-09-0400 PubMedPubMedCentralCrossRefGoogle Scholar
  227. Thai P, Statt S, Chen CH, Liang E, Campbell C, Wu R (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):204–211. doi: 10.1165/rcmb.2013-0159RC PubMedPubMedCentralCrossRefGoogle Scholar
  228. Tian Y, Zhang X, Hao Y, Fang Z, He Y (2014) Potential roles of abnormally expressed long noncoding RNA UCA1 and Malat-1 in metastasis of melanoma. Melanoma Res 24(4):335–341. doi: 10.1097/CMR.0000000000000080 PubMedCrossRefGoogle Scholar
  229. Tiedge H, Chen W, Brosius J (1993) Primary structure, neural-specific expression, and dendritic location of human BC200 RNA. J Neurosci: Official J Soc Neurosci 13(6):2382–2390Google Scholar
  230. Timofeeva MN, Hung RJ, Rafnar T, Christiani DC, Field JK, Bickeboller H, Risch A, McKay JD, Wang Y, Dai J, Gaborieau V, McLaughlin J, Brenner D, Narod SA, Caporaso NE, Albanes D, Thun M, Eisen T, Wichmann HE, Rosenberger A, Han Y, Chen W, Zhu D, Spitz M, Wu X, Pande M, Zhao Y, Zaridze D, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Bencko V, Foretova L, Janout V, Krokan HE, Gabrielsen ME, Skorpen F, Vatten L, Njolstad I, Chen C, Goodman G, Lathrop M, Benhamou S, Vooder T, Valk K, Nelis M, Metspalu A, Raji O, Chen Y, Gosney J, Liloglou T, Muley T, Dienemann H, Thorleifsson G, Shen H, Stefansson K, Brennan P, Amos CI, Houlston R, Landi MT (2012) Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls. Hum Mol Genet 21(22):4980–4995. doi: 10.1093/hmg/dds334 PubMedPubMedCentralCrossRefGoogle Scholar
  231. Tinzl M, Marberger M, Horvath S, Chypre C (2004) DD3PCA3 RNA analysis in urine–a new perspective for detecting prostate cancer. Eur Urol 46(2):182–186; discussion 187. doi: 10.1016/j.eururo.2004.06.004
  232. Tomlinson I, Webb E, Carvajal-Carmona L, Broderick P, Kemp Z, Spain S, Penegar S, Chandler I, Gorman M, Wood W, Barclay E, Lubbe S, Martin L, Sellick G, Jaeger E, Hubner R, Wild R, Rowan A, Fielding S, Howarth K, Silver A, Atkin W, Muir K, Logan R, Kerr D, Johnstone E, Sieber O, Gray R, Thomas H, Peto J, Cazier JB, Houlston R (2007) A genome-wide association scan of tag SNPs identifies a susceptibility variant for colorectal cancer at 8q24.21. Nat Genet 39(8):984–988. doi: 10.1038/ng2085 PubMedCrossRefGoogle Scholar
  233. Trang P, Wiggins JF, Daige CL, Cho C, Omotola M, Brown D, Weidhaas JB, Bader AG, Slack FJ (2011) Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice. Mol Ther: J Am Soc Gene Ther 19(6):1116–1122. doi: 10.1038/mt.2011.48 CrossRefGoogle Scholar
  234. Tripathi V, Ellis JD, Shen Z, Song DY, Pan Q, Watt AT, Freier SM, Bennett CF, Sharma A, Bubulya PA, Blencowe BJ, Prasanth SG, Prasanth KV (2010) The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell 39(6):925–938. doi: 10.1016/j.molcel.2010.08.011 PubMedPubMedCentralCrossRefGoogle Scholar
  235. Tripathi V, Shen Z, Chakraborty A, Giri S, Freier SM, Wu X, Zhang Y, Gorospe M, Prasanth SG, Lal A, Prasanth KV (2013) Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet 9(3):e1003368. doi: 10.1371/journal.pgen.1003368 PubMedPubMedCentralCrossRefGoogle Scholar
  236. Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329(5992):689–693. doi: 10.1126/science.1192002 PubMedPubMedCentralCrossRefGoogle Scholar
  237. Tsai MC, Spitale RC, Chang HY (2011) Long intergenic noncoding RNAs: new links in cancer progression. Cancer Res 71(1):3–7. doi: 10.1158/0008-5472.CAN-10-2483 PubMedPubMedCentralCrossRefGoogle Scholar
  238. Tsang WP, Wong TW, Cheung AH, Co CN, Kwok TT (2007) Induction of drug resistance and transformation in human cancer cells by the noncoding RNA CUDR. RNA 13(6):890–898. doi: 10.1261/rna.359007
  239. Tseng YY, Moriarity BS, Gong W, Akiyama R, Tiwari A, Kawakami H, Ronning P, Reuland B, Guenther K, Beadnell TC, Essig J, Otto GM, O'Sullivan MG, Largaespada DA, Schwertfeger KL, Marahrens Y, Kawakami Y, Bagchi A (2014) PVT1 dependence in cancer with MYC copy-number increase. Nature 512(7512):82–86. doi: 10.1038/nature13311 PubMedPubMedCentralGoogle Scholar
  240. Tsichlis PN, Strauss PG, Hu LF (1983) A common region for proviral DNA integration in MoMuLV-induced rat thymic lymphomas. Nature 302(5907):445–449PubMedCrossRefGoogle Scholar
  241. Tsichlis PN, Shepherd BM, Bear SE (1989) Activation of the Mlvi-1/mis1/pvt-1 locus in Moloney murine leukemia virus-induced T-cell lymphomas. Proc Natl Acad Sci USA 86(14):5487–5491PubMedPubMedCentralCrossRefGoogle Scholar
  242. Tu ZQ, Li RJ, Mei JZ, Li XH (2014) Down-regulation of long non-coding RNA GAS5 is associated with the prognosis of hepatocellular carcinoma. Int J Clin Exp Pathol 7(7):4303–4309PubMedPubMedCentralGoogle Scholar
  243. Tuupanen S, Turunen M, Lehtonen R, Hallikas O, Vanharanta S, Kivioja T, Bjorklund M, Wei G, Yan J, Niittymaki I, Mecklin JP, Jarvinen H, Ristimaki A, Di-Bernardo M, East P, Carvajal-Carmona L, Houlston RS, Tomlinson I, Palin K, Ukkonen E, Karhu A, Taipale J, Aaltonen LA (2009) The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nat Genet 41(8):885–890. doi: 10.1038/ng.406 PubMedCrossRefGoogle Scholar
  244. Ulaner GA, Vu TH, Li T, Hu JF, Yao XM, Yang Y, Gorlick R, Meyers P, Healey J, Ladanyi M, Hoffman AR (2003) Loss of imprinting of IGF2 and H19 in osteosarcoma is accompanied by reciprocal methylation changes of a CTCF-binding site. Hum Mol Genet 12(5):535–549PubMedCrossRefGoogle Scholar
  245. Uno S, Zembutsu H, Hirasawa A, Takahashi A, Kubo M, Akahane T, Aoki D, Kamatani N, Hirata K, Nakamura Y (2010) A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese. Nat Genet 42(8):707–710. doi: 10.1038/ng.612 PubMedCrossRefGoogle Scholar
  246. U.S. Department of Health and Human Services (2010) How tobacco smoke causes disease: the biology and behavioral basis for smoking-attributable disease: a report of the surgeon general. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; National Center for Chronic Disease Prevention and Health Promotion; Office on Smoking and Health, Atlanta, GAGoogle Scholar
  247. Villeneuve L, Rassart E, Jolicoeur P, Graham M, Adams JM (1986) Proviral integration site Mis-1 in rat thymomas corresponds to the pvt-1 translocation breakpoint in murine plasmacytomas. Mol Cell Biol 6(5):1834–1837PubMedPubMedCentralCrossRefGoogle Scholar
  248. Wahlestedt C (2013) Targeting long non-coding RNA to therapeutically upregulate gene expression. Nat Rev Drug Discov 12(6):433–446. doi: 10.1038/nrd4018 PubMedCrossRefGoogle Scholar
  249. Wan G, Mathur R, Hu X, Liu Y, Zhang X, Peng G, Lu X (2013) Long non-coding RNA ANRIL (CDKN2B-AS) is induced by the ATM-E2F1 signaling pathway. Cell Signal 25(5):1086–1095. doi: 10.1016/j.cellsig.2013.02.006 PubMedPubMedCentralCrossRefGoogle Scholar
  250. Wang KC, Chang HY (2011) Molecular mechanisms of long noncoding RNAs. Mol Cell 43(6):904–914. doi: 10.1016/j.molcel.2011.08.018 PubMedPubMedCentralCrossRefGoogle Scholar
  251. Wang XS, Zhang Z, Wang HC, Cai JL, Xu QW, Li MQ, Chen YC, Qian XP, Lu TJ, Yu LZ, Zhang Y, Xin DQ, Na YQ, Chen WF (2006) Rapid identification of UCA1 as a very sensitive and specific unique marker for human bladder carcinoma. Clin Cancer Res: Official J Am Assoc Cancer Res 12(16):4851–4858. doi: 10.1158/1078-0432.CCR-06-0134 CrossRefGoogle Scholar
  252. Wang F, Li X, Xie X, Zhao L, Chen W (2008) UCA1, a non-protein-coding RNA up-regulated in bladder carcinoma and embryo, influencing cell growth and promoting invasion. FEBS Lett 582(13):1919–1927. doi: 10.1016/j.febslet.2008.05.012 PubMedCrossRefGoogle Scholar
  253. Wang P, Ren Z, Sun P (2012a) Overexpression of the long non-coding RNA MEG3 impairs in vitro glioma cell proliferation. J Cell Biochem 113(6):1868–1874. doi: 10.1002/jcb.24055 PubMedCrossRefGoogle Scholar
  254. Wang Y, Chen W, Yang C, Wu W, Wu S, Qin X, Li X (2012b) Long non-coding RNA UCA1a(CUDR) promotes proliferation and tumorigenesis of bladder cancer. Int J Oncol 41(1):276–284. doi: 10.3892/ijo.2012.1443 PubMedGoogle Scholar
  255. Wang F, Yuan JH, Wang SB, Yang F, Yuan SX, Ye C, Yang N, Zhou WP, Li WL, Li W, Sun SH (2014a) Oncofetal long noncoding RNA PVT1 promotes proliferation and stem cell-like property of hepatocellular carcinoma cells by stabilizing NOP2. Hepatol 60(4):1278–1290. doi: 10.1002/hep.27239
  256. Wang X, Gong Y, Jin B, Wu C, Yang J, Wang L, Zhang Z, Mao Z (2014b) Long non-coding RNA urothelial carcinoma associated 1 induces cell replication by inhibiting BRG1 in 5637 cells. Oncol Rep 32(3):1281–1290. doi: 10.3892/or.2014.3309 PubMedPubMedCentralGoogle Scholar
  257. Wang Y, Guo Q, Zhao Y, Chen J, Wang S, Hu J, Sun Y (2014c) BRAF-activated long non-coding RNA contributes to cell proliferation and activates autophagy in papillary thyroid carcinoma. Oncol Lett 8(5):1947–1952. doi: 10.3892/ol.2014.2487 PubMedPubMedCentralGoogle Scholar
  258. Wang Y, Chen W, Chen J, Pan Q, Pan J (2014d) LncRNA expression profiles of EGFR exon 19 deletions in lung adenocarcinoma ascertained by using microarray analysis. Med Oncol 31(9):137. doi: 10.1007/s12032-014-0137-y
  259. Wang Y, Xu G, Chen W, Pan Q, Huang K, Pan J, Zhang W, Chen J (2014e) Detection of long-chain non-encoding RNA differential expression in non-small cell lung cancer by microarray analysis and preliminary verification. Mol Med Rep. doi: 10.3892/mmr.2014.2944 Google Scholar
  260. Watson JB, Sutcliffe JG (1987) Primate brain-specific cytoplasmic transcript of the Alu repeat family. Mol Cell Biol 7(9):3324–3327PubMedPubMedCentralCrossRefGoogle Scholar
  261. Webb E, Adams JM, Cory S (1984) Variant (6; 15) translocation in a murine plasmacytoma occurs near an immunoglobulin kappa gene but far from the myc oncogene. Nature 312(5996):777–779PubMedCrossRefGoogle Scholar
  262. White NM, Cabanski CR, Silva-Fisher JM, Dang HX, Govindan R, Maher CA (2014) Transcriptome sequencing reveals altered long intergenic non-coding RNAs in lung cancer. Genome Biol 15(8):429. doi: 10.1186/s13059-014-0429-8 PubMedPubMedCentralCrossRefGoogle Scholar
  263. Whiteside EJ, Seim I, Pauli JP, O'Keeffe AJ, Thomas PB, Carter SL, Walpole CM, Fung JN, Josh P, Herington AC, Chopin LK (2013) Identification of a long non-coding RNA gene, growth hormone secretagogue receptor opposite strand, which stimulates cell migration in non-small cell lung cancer cell lines. Int J Oncol 43(2):566–574. doi: 10.3892/ijo.2013.1969 PubMedGoogle Scholar
  264. Wiggs JL, Yaspan BL, Hauser MA, Kang JH, Allingham RR, Olson LM, Abdrabou W, Fan BJ, Wang DY, Brodeur W, Budenz DL, Caprioli J, Crenshaw A, Crooks K, Delbono E, Doheny KF, Friedman DS, Gaasterland D, Gaasterland T, Laurie C, Lee RK, Lichter PR, Loomis S, Liu Y, Medeiros FA, McCarty C, Mirel D, Moroi SE, Musch DC, Realini A, Rozsa FW, Schuman JS, Scott K, Singh K, Stein JD, Trager EH, Vanveldhuisen P, Vollrath D, Wollstein G, Yoneyama S, Zhang K, Weinreb RN, Ernst J, Kellis M, Masuda T, Zack D, Richards JE, Pericak-Vance M, Pasquale LR, Haines JL (2012) Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma. PLoS Genet 8(4):e1002654. doi: 10.1371/journal.pgen.1002654 PubMedPubMedCentralCrossRefGoogle Scholar
  265. Wilusz JE, Freier SM, Spector DL (2008) 3’ end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell 135(5):919–932. doi: 10.1016/j.cell.2008.10.012 PubMedPubMedCentralCrossRefGoogle Scholar
  266. Winter J, Jung S, Keller S, Gregory RI, Diederichs S (2009) Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 11(3):228–234. doi: 10.1038/ncb0309-228 PubMedCrossRefGoogle Scholar
  267. Wu Y, Crawford M, Yu B, Mao Y, Nana-Sinkam SP, Lee LJ (2011) MicroRNA delivery by cationic lipoplexes for lung cancer therapy. Mol Pharm 8(4):1381–1389. doi: 10.1021/mp2002076 PubMedPubMedCentralCrossRefGoogle Scholar
  268. Wu W, Zhang S, Li X, Xue M, Cao S, Chen W (2013a) Ets-2 regulates cell apoptosis via the Akt pathway, through the regulation of urothelial cancer associated 1, a long non-coding RNA, in bladder cancer cells. PLoS ONE 8(9):e73920. doi: 10.1371/journal.pone.0073920 PubMedPubMedCentralCrossRefGoogle Scholar
  269. Wu Y, Crawford M, Mao Y, Lee RJ, Davis IC, Elton TS, Lee LJ, Nana-Sinkam SP (2013b) Therapeutic delivery of MicroRNA-29b by cationic lipoplexes for lung cancer. Mol Ther Nucleic Acids 2:e84. doi: 10.1038/mtna.2013.14 PubMedPubMedCentralCrossRefGoogle Scholar
  270. Xiang JF, Yin QF, Chen T, Zhang Y, Zhang XO, Wu Z, Zhang S, Wang HB, Ge J, Lu X, Yang L, Chen LL (2014) Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus. Cell Res 24(5):513–531. doi: 10.1038/cr.2014.35 PubMedPubMedCentralCrossRefGoogle Scholar
  271. Xie HW, Wu QQ, Zhu B, Chen FJ, Ji L, Li SQ, Wang CM, Tong YS, Tuo L, Wu M, Liu ZH, Lv J, Shi WH, Cao XF (2014) Long noncoding RNA SPRY4-IT1 is upregulated in esophageal squamous cell carcinoma and associated with poor prognosis. Tumour Biol: J Int Soc Oncodevelopmental Biol Med 35(8):7743–7754. doi: 10.1007/s13277-014-2013-y CrossRefGoogle Scholar
  272. Xu Y, Wang J, Qiu M, Xu L, Li M, Jiang F, Yin R (2014) Upregulation of the long noncoding RNA TUG1 promotes proliferation and migration of esophageal squamous cell carcinoma. Tumour Biol: J Int Soc Oncodevelopmental Biol Med. doi: 10.1007/s13277-014-2763-6 Google Scholar
  273. Xue M, Li X, Li Z, Chen W (2014a) Urothelial carcinoma associated 1 is a hypoxia-inducible factor-1alpha-targeted long noncoding RNA that enhances hypoxic bladder cancer cell proliferation, migration, and invasion. Tumour Biol: J Int Soc Oncodevelopmental Biol Med 35(7):6901–6912. doi: 10.1007/s13277-014-1925-x CrossRefGoogle Scholar
  274. Xue M, Li X, Wu W, Zhang S, Wu S, Li Z, Chen W (2014b) Upregulation of long non-coding RNA urothelial carcinoma associated 1 by CCAAT/enhancer binding protein alpha contributes to bladder cancer cell growth and reduced apoptosis. Oncol Rep 31(5):1993–2000. doi: 10.3892/or.2014.3092 PubMedPubMedCentralGoogle Scholar
  275. Yang F, Zhang L, Huo XS, Yuan JH, Xu D, Yuan SX, Zhu N, Zhou WP, Yang GS, Wang YZ, Shang JL, Gao CF, Zhang FR, Wang F, Sun SH (2011a) Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans. Hepatology 54(5):1679–1689. doi: 10.1002/hep.24563
  276. Yang L, Lin C, Liu W, Zhang J, Ohgi KA, Grinstein JD, Dorrestein PC, Rosenfeld MG (2011b) ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell 147(4):773–788. doi: 10.1016/j.cell.2011.08.054 PubMedPubMedCentralCrossRefGoogle Scholar
  277. Yang Z, Zhou L, Wu LM, Lai MC, Xie HY, Zhang F, Zheng SS (2011c) Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol 18(5):1243–1250. doi: 10.1245/s10434-011-1581-y PubMedCrossRefGoogle Scholar
  278. Yang F, Bi J, Xue X, Zheng L, Zhi K, Hua J, Fang G (2012) Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells. The FEBS J 279(17):3159–3165. doi: 10.1111/j.1742-4658.2012.08694.x PubMedCrossRefGoogle Scholar
  279. Yang F, Huo XS, Yuan SX, Zhang L, Zhou WP, Wang F, Sun SH (2013a) Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis. Mol Cell 49(6):1083–1096. doi: 10.1016/j.molcel.2013.01.010 PubMedCrossRefGoogle Scholar
  280. Yang F, Xue X, Bi J, Zheng L, Zhi K, Gu Y, Fang G (2013b) Long noncoding RNA CCAT1, which could be activated by c-Myc, promotes the progression of gastric carcinoma. J Cancer Res Clin Oncol 139(3):437–445. doi: 10.1007/s00432-012-1324-x PubMedCrossRefGoogle Scholar
  281. Yang F, Yi F, Han X, Du Q, Liang Z (2013c) MALAT-1 interacts with hnRNP C in cell cycle regulation. FEBS Lett 587(19):3175–3181. doi: 10.1016/j.febslet.2013.07.048 PubMedCrossRefGoogle Scholar
  282. Yang G, Lu X, Yuan L (2014a) LncRNA: a link between RNA and cancer. Biochimica et biophysica acta 1839(11):1097–1109. doi: 10.1016/j.bbagrm.2014.08.012
  283. Yang J, Lin J, Liu T, Chen T, Pan S, Huang W, Li S (2014b) Analysis of lncRNA expression profiles in non-small cell lung cancers (NSCLC) and their clinical subtypes. Lung Cancer 85(2):110–115. doi: 10.1016/j.lungcan.2014.05.011 PubMedCrossRefGoogle Scholar
  284. Yang YR, Zang SZ, Zhong CL, Li YX, Zhao SS, Feng XJ (2014c) Increased expression of the lncRNA PVT1 promotes tumorigenesis in non-small cell lung cancer. Int J Clin Exp Pathol 7(10):6929–6935PubMedPubMedCentralGoogle Scholar
  285. Yao Y, Li J, Wang L (2014) Large intervening non-coding RNA HOTAIR is an indicator of poor prognosis and a therapeutic target in human cancers. Int J Mol Sci 15(10):18985–18999. doi: 10.3390/ijms151018985 PubMedPubMedCentralCrossRefGoogle Scholar
  286. Yap KL, Li S, Munoz-Cabello AM, Raguz S, Zeng L, Mujtaba S, Gil J, Walsh MJ, Zhou MM (2010) Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell 38(5):662–674. doi: 10.1016/j.molcel.2010.03.021 PubMedPubMedCentralCrossRefGoogle Scholar
  287. Yin D, He X, Zhang E, Kong R, De W, Zhang Z (2014) Long noncoding RNA GAS5 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer. Med Oncol 31(11):253. doi: 10.1007/s12032-014-0253-8
  288. Yoshimizu T, Miroglio A, Ripoche MA, Gabory A, Vernucci M, Riccio A, Colnot S, Godard C, Terris B, Jammes H, Dandolo L (2008) The H19 locus acts in vivo as a tumor suppressor. Proc Natl Acad Sci USA 105(34):12417–12422. doi: 10.1073/pnas.0801540105 PubMedPubMedCentralCrossRefGoogle Scholar
  289. You L, Chang D, Du HZ, Zhao YP (2011) Genome-wide screen identifies PVT1 as a regulator of gemcitabine sensitivity in human pancreatic cancer cells. Biochem Biophys Res Commun 407(1):1–6. doi: 10.1016/j.bbrc.2011.02.027 PubMedCrossRefGoogle Scholar
  290. Young TL, Matsuda T, Cepko CL (2005) The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina. Curr Biol CB 15(6):501–512. doi: 10.1016/j.cub.2005.02.027 PubMedCrossRefGoogle Scholar
  291. Yuan SX, Yang F, Yang Y, Tao QF, Zhang J, Huang G, Wang RY, Yang S, Huo XS, Zhang L, Wang F, Sun SH, Zhou WP (2012) Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients’ poor recurrence-free survival after hepatectomy. Hepatology 56(6):2231–2241. doi: 10.1002/hep.25895
  292. Zemel S, Bartolomei MS, Tilghman SM (1992) Physical linkage of two mammalian imprinted genes, H19 and insulin-like growth factor 2. Nat Genet 2(1):61–65. doi: 10.1038/ng0992-61 PubMedCrossRefGoogle Scholar
  293. Zhang Y, Tycko B (1992) Monoallelic expression of the human H19 gene. Nat Genet 1(1):40–44. doi: 10.1038/ng0492-40 PubMedCrossRefGoogle Scholar
  294. Zhang X, Zhou Y, Mehta KR, Danila DC, Scolavino S, Johnson SR, Klibanski A (2003) A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells. J Clin Endocrinol Metab 88(11):5119–5126. doi: 10.1210/jc.2003-030222 PubMedCrossRefGoogle Scholar
  295. Zhang Y, Lu Y, Yuan BZ, Castranova V, Shi X, Stauffer JL, Demers LM, Chen F (2005) The human mineral dust-induced gene, mdig, is a cell growth regulating gene associated with lung cancer. Oncogene 24(31):4873–4882. doi: 10.1038/sj.onc.1208668 PubMedCrossRefGoogle Scholar
  296. Zhang S, Chen L, Jung EJ, Calin GA (2010a) Targeting microRNAs with small molecules: from dream to reality. Clin Pharmacol Ther 87(6):754–758. doi: 10.1038/clpt.2010.46 PubMedPubMedCentralCrossRefGoogle Scholar
  297. Zhang X, Rice K, Wang Y, Chen W, Zhong Y, Nakayama Y, Zhou Y, Klibanski A (2010b) Maternally expressed gene 3 (MEG3) noncoding ribonucleic acid: isoform structure, expression, and functions. Endocrinology 151(3):939–947. doi: 10.1210/en.2009-0657 PubMedPubMedCentralCrossRefGoogle Scholar
  298. Zhang X, Zhou Y, Klibanski A (2010c) Isolation and characterization of novel pituitary tumor related genes: a cDNA representational difference approach. Mol Cell Endocrinol 326(1–2):40–47. doi: 10.1016/j.mce.2010.02.040 PubMedPubMedCentralCrossRefGoogle Scholar
  299. Zhang B, Arun G, Mao YS, Lazar Z, Hung G, Bhattacharjee G, Xiao X, Booth CJ, Wu J, Zhang C, Spector DL (2012) The lncRNA Malat1 is dispensable for mouse development but its transcription plays a cis-regulatory role in the adult. Cell Rep 2(1):111–123. doi: 10.1016/j.celrep.2012.06.003 PubMedPubMedCentralCrossRefGoogle Scholar
  300. Zhang JX, Han L, Bao ZS, Wang YY, Chen LY, Yan W, Yu SZ, Pu PY, Liu N, You YP, Jiang T, Kang CS (2013a) HOTAIR, a cell cycle-associated long noncoding RNA and a strong predictor of survival, is preferentially expressed in classical and mesenchymal glioma. Neuro-Oncol 15(12):1595–1603. doi: 10.1093/neuonc/not131 PubMedPubMedCentralCrossRefGoogle Scholar
  301. Zhang L, Yang F, Yuan JH, Yuan SX, Zhou WP, Huo XS, Xu D, Bi HS, Wang F, Sun SH (2013b) Epigenetic activation of the MiR-200 family contributes to H19-mediated metastasis suppression in hepatocellular carcinoma. Carcinogenesis 34(3):577–586. doi: 10.1093/carcin/bgs381 PubMedCrossRefGoogle Scholar
  302. Zhang Q, Geng PL, Yin P, Wang XL, Jia JP, Yao J (2013c) Down-regulation of long non-coding RNA TUG1 inhibits osteosarcoma cell proliferation and promotes apoptosis. Asian Pac J Cancer Prev: APJCP 14(4):2311–2315PubMedCrossRefGoogle Scholar
  303. Zhang Z, Zhu Z, Watabe K, Zhang X, Bai C, Xu M, Wu F, Mo YY (2013d) Negative regulation of lncRNA GAS5 by miR-21. Cell Death Differ 20(11):1558–1568. doi: 10.1038/cdd.2013.110 PubMedPubMedCentralCrossRefGoogle Scholar
  304. Zhang EB, Kong R, Yin DD, You LH, Sun M, Han L, Xu TP, Xia R, Yang JS, De W, Chen J (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
  305. Zhang EB, Yin DD, Sun M, Kong R, Liu XH, You LH, Han L, Xia R, Wang KM, Yang JS, De W, Shu YQ, Wang ZX (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:e1243. doi: 10.1038/cddis.2014.201 PubMedPubMedCentralCrossRefGoogle Scholar
  306. Zhang HM, Yang FQ, Chen SJ, Che J, Zheng JH (2014c) Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma. Tumour Biol: J Int Soc Oncodevelopmental Biol Med. doi: 10.1007/s13277-014-2925-6 Google Scholar
  307. Zhang HM, Yang FQ, Yan Y, Che JP, Zheng JH (2014d) High expression of long non-coding RNA SPRY4-IT1 predicts poor prognosis of clear cell renal cell carcinoma. Int J Clin Exp Pathol 7(9):5801–5809PubMedPubMedCentralGoogle Scholar
  308. Zhang K, Shi ZM, Chang YN, Hu ZM, Qi HX, Hong W (2014e) The ways of action of long non-coding RNAs in cytoplasm and nucleus. Gene 547(1):1–9. doi: 10.1016/j.gene.2014.06.043 PubMedCrossRefGoogle Scholar
  309. Zhang L, Zhou XF, Pan GF, Zhao JP (2014f) Enhanced expression of long non-coding RNA ZXF1 promoted the invasion and metastasis in lung adenocarcinoma. Biomed Pharmacother Biomed Pharmacotherapie 68(4):401–407. doi: 10.1016/j.biopha.2014.03.001
  310. Zhao J, Dahle D, Zhou Y, Zhang X, Klibanski A (2005) Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors. J Clin Endocrinol Metab 90(4):2179–2186. doi: 10.1210/jc.2004-1848 PubMedCrossRefGoogle Scholar
  311. Zhao W, Luo J, Jiao S (2014) Comprehensive characterization of cancer subtype associated long non-coding RNAs and their clinical implications. Sci Rep 4:6591. doi: 10.1038/srep06591 PubMedPubMedCentralCrossRefGoogle Scholar
  312. Zhou Y, Zhong Y, Wang Y, Zhang X, Batista DL, Gejman R, Ansell PJ, Zhao J, Weng C, Klibanski A (2007) Activation of p53 by MEG3 non-coding RNA. J Biol Chem 282(34):24731–24742. doi: 10.1074/jbc.M702029200 PubMedCrossRefGoogle Scholar
  313. Zhou Y, Cheunsuchon P, Nakayama Y, Lawlor MW, Zhong Y, Rice KA, Zhang L, Zhang X, Gordon FE, Lidov HG, Bronson RT, Klibanski A (2010) Activation of paternally expressed genes and perinatal death caused by deletion of the Gtl2 gene. Development 137(16):2643–2652. doi: 10.1242/dev.045724 PubMedPubMedCentralCrossRefGoogle Scholar
  314. Zhou Y, Zhang X, Klibanski A (2012) MEG3 noncoding RNA: a tumor suppressor. J Mol Endocrinol 48(3):R45–R53. doi: 10.1530/JME-12-0008 PubMedPubMedCentralCrossRefGoogle Scholar
  315. Zhuang Y, Wang X, Nguyen HT, Zhuo Y, Cui X, Fewell C, Flemington EK, Shan B (2013) Induction of long intergenic non-coding RNA HOTAIR in lung cancer cells by type I collagen. J Hematol Oncol 6:35. doi: 10.1186/1756-8722-6-35 PubMedPubMedCentralCrossRefGoogle Scholar
  316. Zou Y, Jiang Z, Yu X, Sun M, Zhang Y, Zuo Q, Zhou J, Yang N, Han P, Ge Z, De W, Sun L (2013) Upregulation of long noncoding RNA SPRY4-IT1 modulates proliferation, migration, apoptosis, and network formation in trophoblast cells HTR-8SV/neo. PLoS ONE 8(11):e79598. doi: 10.1371/journal.pone.0079598 PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Division of RNA Biology and Cancer, German Cancer Research Center (DKFZ) and Institute of PathologyUniversity Hospital HeidelbergHeidelbergGermany

Personalised recommendations