Molecular Biology

, Volume 52, Issue 6, pp 787–798 | Cite as

Long Noncoding RNAs and Their Role in Oncogenesis

  • I. V. Bure
  • E. B. Kuznetsova
  • D. V. ZaletaevEmail author


The noncoding part of the human genome, which was previously considered nonfunctional or junk DNA, has been the subject of extensive research this decade. Nevertheless, long noncoding RNAs still represent one of the least investigated fields because of their complexity, multiplicity, and diversity. While some long noncoding RNAs have been characterized fairly well, the functions of many others remain poorly understood. Long noncoding RNAs play an essential role in the regulation of gene expression in all tissues and on all developmental stages. They are involved in a number of signaling pathways, and their aberrant functioning can be pathogenic. This review aims to summarize current state-of-the-art structures of these transcripts in this research field, their genomic localization, their functions, and underlying mechanisms. It also focuses on cancer-associated aberrations of long noncoding RNAs, as well as on prospects of their application in tumor diagnostics and therapy. Examples of decreasing the levels of oncogenic long noncoding RNAs via silencing with short interfering RNAs, antisense oligonucleotides, or low molecular-weight inhibitors are also described.


long noncoding RNAs oncogenesis diagnostics regulation 



  1. 1.
    Mercer T.R., Mattick J.S. 2013. Structure and function of long noncoding RNAs in epigenetic regulation. Nat. Struct. Mol. Biol. 20, 300‒307.CrossRefPubMedGoogle Scholar
  2. 2.
    Taft R.J., Pheasant M., Mattick J.S. 2007. The relationship between non-protein-coding DNA and eukaryotic complexity. Bioessays. 29, 288‒299.CrossRefPubMedGoogle Scholar
  3. 3.
    Bunch H. 2018. Gene regulation of mammalian long non-coding RNA. Mol. Genet. Genomics. 293, 1‒15.CrossRefPubMedGoogle Scholar
  4. 4.
    Djebali S., Davis C.A., Merkel A., Dobin A., Lassmann T., Mortazavi A., Tanzer A., Lagarde J., Lin W., Schlesinger F., Xue C., Marinov G.K., Khatun J., Williams B.A., Zaleski C., et al. 2012. Landscape of transcription in human cells. Nature. 489, 101‒108.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Yang G., Lu X., Yuan L. 2014. LncRNA: A link between RNA and cancer. Biochim. Biophys. Acta. 1839, 1097‒1109.CrossRefPubMedGoogle Scholar
  6. 6.
    Makarova J.A., Kramerov D.A. 2007. Noncoding RNAs. Biochemistry (Moscow). 72 (11), 1161–1178.PubMedGoogle Scholar
  7. 7.
    Hall A.E., Turnbull C., Dalmay T. 2013. Y RNAs: Recent developments. Biomol. Concepts. 4, 103‒110.CrossRefPubMedGoogle Scholar
  8. 8.
    Guttman M., Rinn J.L. 2012. Modular regulatory principles of large non-coding RNAs. Nature. 482, 339‒346.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Bratkovic T., Rogelj B. 2014. The many faces of small nucleolar RNAs. Biochim. Biophys Acta. 1839, 438‒443.CrossRefPubMedGoogle Scholar
  10. 10.
    Falaleeva M., Welden J.R., Duncan M.J., Stammet S. 2017. C/D-box snoRNAs form methylating and non-methylating ribonucleoprotein complexes: Old dogs show new tricks. Bioessays. 39, 1‒15.CrossRefGoogle Scholar
  11. 11.
    Makarova J.A., Ivanova S.M., Tonevitsky A.G., Gri-goriev A.I. 2013. New functions of small nucleolar RNAs. Biochemistry (Moscow). 78 (6), 638–650.PubMedGoogle Scholar
  12. 12.
    Ulitsky I., Bartel D.P. 2013. lincRNAs: Genomics, evolution, and mechanisms. Cell. 154, 26‒46.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Wang K.C., Chang H.Y. 2011. Molecular mechanisms of long noncoding RNAs. Mol. Cell. 43, 904‒914.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Derrien T., Johnson R., Bussotti G., Tanzer A., Djebali S., Tilgner H., Guernec G., Martin D., Merkel A., Knowles D.G., Lagarde J., Veeravalli L., Ruan X., Ruan Y., Lassmann T., et al. 2012. The GENCODE v. 7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression. Genome Res. 22, 1775‒1789.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Bunch H., Lawney B.P., Burkholder A., Ma D., Zheng X., Motola S., Fargo D.C., Levine S.S., Wang Y.E., Hu G. 2016. RNA polymerase II promoter-proximal pausing in mammalian long non-coding genes. Genomics. 108, 64‒77.CrossRefPubMedGoogle Scholar
  16. 16.
    Guenzl P.M., Barlow D.P. 2012. Macro lncRNAs: A new layer of cis-regulatory information in the mammalian genome. RNA Biol. 9, 731‒741.CrossRefPubMedGoogle Scholar
  17. 17.
    St Laurent G., Vyatkin Y., Antonets D., Ri M., Qi Y., Saik O., Shtokalo D., de Hoon M.J., Kawaji H., Itoh M., Lassmann T., Arner E., Forrest A.R.; FANTOM consortium; Nicolas E., McCaffrey T.A., et al. 2016. Functional annotation of the vlinc class of non-coding RNAs using systems biology approach. Nucleic Acids Res. 44, 3233‒3252.CrossRefPubMedGoogle Scholar
  18. 18.
    Wu T., Du Y. 2017. LncRNAs: From basic research to medical application. Int. J. Biol. Sci. 13, 295‒307.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Brannan C.I., Dees E.C., Ingram R.S., Tilghman S.M. 1990. The product of the H19 gene may function as an RNA. Mol. Cell. Biol. 10, 28‒36.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Pachnis V., Belayew A., Tilghman S.M. 1984. Locus unlinked to alpha-fetoprotein under the control of the murine raf and Rif genes. Proc. Natl. Acad. Sci. U. S. A. 81, 5523‒5527.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Brown C.J., Ballabio A., Rupert J.L., Lafreniere R.G., Grompe M., Tonlorenzi R., Willard H.F. 1991. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature. 349, 38‒44.CrossRefPubMedGoogle Scholar
  22. 22.
    Hu X., Sood A.K., Dang C.V., Zhang L. 2018. The role of long noncoding RNAs in cancer: The dark matter matters. Curr. Opin. Genet. Dev. 48, 8‒15.CrossRefPubMedGoogle Scholar
  23. 23.
    Iyer M.K., Niknafs Y.S., Malik R., Singhal U., Sahu A., Hosono Y., Barrette T.R., Prensner J.R., Evans J.R., Zhao S., Poliakov A., Cao X., Dhanasekaran S.M., Wu Y.M., Robinson D.R., et al. 2015. The landscape of long noncoding RNAs in the human transcriptome. Nat. Genet. 47, 199‒208.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Zhao Y., Li H., Fang S., Kang Y., Wu W., Hao Y., Li Z., Bu D., Sun N., Zhang M.Q., Chen R. 2016. NONCODE 2016: An informative and valuable data source of long non-coding RNAs. Nucleic Acids Res. 44, D203‒D208.CrossRefPubMedGoogle Scholar
  25. 25.
    Volders P.J., Helsens K., Wang X., Menten B., Martens L., Gevaert K., Vandesompele J., Mestdagh P. 2013. LNCipedia: A database for annotated human lncRNA transcript sequences and structures. Nucleic Acids Res. 41, D246‒251.CrossRefPubMedGoogle Scholar
  26. 26.
    Quek X.C., Thomson D.W., Maag J.L., Bartonicek N., Signal B., Clark M.B., Gloss B.S., Dinger M.E. 2015. lncRNAdb v. 2.0: Expanding the reference database for functional long noncoding RNAs. Nucleic Acids Res. 43, D168‒D173.CrossRefPubMedGoogle Scholar
  27. 27.
    Housman G., Ulitsky I. 2016. Methods for distinguishing between protein-coding and long noncoding RNAs and the elusive biological purpose of translation of long noncoding RNAs. Biochim. Biophys. Acta. 1859, 31‒40.CrossRefPubMedGoogle Scholar
  28. 28.
    Slavoff S.A., Mitchell A.J., Schwaid A.G., Cabili M.N., Ma J., Levin J.Z., Karger A.D., Budnik B.A., Rinn J.L., Saghatelian A. 2013. Peptidomic discovery of short open reading frame-encoded peptides in human cells. Nat. Chem. Biol. 9, 59‒64.CrossRefPubMedGoogle Scholar
  29. 29.
    Matsumoto A., Pasut A., Matsumoto M., Yamashita R., Fung J., Monteleone E., Saghatelian A., Nakayama K.I., Clohessy J.G., Pandolfi P.P. 2017. mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide. Nature. 541, 228‒232.CrossRefPubMedGoogle Scholar
  30. 30.
    Nelson B.R., Makarewich C.A., Anderson D.M., Winders B.R., Troupes C.D., Wu F., Reese A.L., McAnally J.R., Chen X., Kavalali E.T., Cannon S.C., Houser S.R., Bassel-Duby R., Olson E.N. 2016. A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle. Science. 351, 271‒275.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Sigova A.A., Mullen A.C., Molinie B., Gupta S., Orlando D.A., Guenther M.G., Almada A.E., Lin C., Sharp P.A., Giallourakis C.C., Young R.A. 2013. Divergent transcription of long noncoding RNA/ mRNA gene pairs in embryonic stem cells. Proc. Natl. Acad. Sci. U. S. A. 110, 2876‒2881.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Quinn J.J., Chang H.Y. 2016. Unique features of long non-coding RNA biogenesis and function. Nat. Rev. Genet. 17, 47‒62.CrossRefPubMedGoogle Scholar
  33. 33.
    Yang L., Duff M.O., Graveley B.R., Carmichael G.G., Chen L.L. 2011. Genome-wide characterization of non-polyadenylated RNAs. Genome Biol. 12, R16.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Samudyata Castelo-Branco G., Bonetti A. 2017. Birth, coming of age and death: The intriguing life of long noncoding RNAs. Semin. Cell Dev. Biol. pii: S1084-9521(17)30250-1. doi 10.1016/j.semcdb.2017.11.012Google Scholar
  35. 35.
    Diederichs S. 2014. The four dimensions of noncoding RNA conservation. Trends Genet. 30, 121‒123.CrossRefPubMedGoogle Scholar
  36. 36.
    Hezroni H., Koppstein D., Schwartz M.G., Avrutin A., Bartel D.P., Ulitsky I. 2015. Principles of long noncoding RNA evolution derived from direct comparison of transcriptomes in 17 species. Cell Rep. 11, 1110‒1122.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Li R., Zhu H., Luo Y. 2016. Understanding the functions of long non-coding RNAs through their higher-order structures. Int. J. Mol. Sci. 17 (5), pii: E702. doi 10.3390/ijms17050702CrossRefPubMedGoogle Scholar
  38. 38.
    Guttman M., Guan D., Fan Q., Su J., Zheng W., Ma W., Ke C. 2009. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 458, 223‒227.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Mattick J.S., Rinn J.L. 2015. Discovery and annotation of long noncoding RNAs. Nat. Struct. Mol. Biol. 22, 5‒7.CrossRefPubMedGoogle Scholar
  40. 40.
    He Y., Vogelstein B., Velculescu V.E., Papadopoulos N., Kinzler K.W. 2008. The antisense transcriptomes of human cells. Science. 322, 1855‒1857.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Scruggs B.S., Gilchrist D.A., Nechaev S., Muse G.W., Burkholder A., Fargo D.C., Adelman K. 2015. Bidirectional transcription arises from two distinct hubs of transcription factor binding and active chromatin. Mol. Cell. 58, 1101‒1112.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Wei W., Pelechano V., Järvelin A.I., Steinmetz L.M. 2011. Functional consequences of bidirectional promoters. Trends Genet. 27, 267‒276.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Lepoivre C., Belhocine M., Bergon A., Griffon A., Yammine M., Vanhille L., Zacarias-Cabeza J., Garibal M.A., Koch F., Maqbool M.A., Fenouil R., Loriod B., Holota H., Gut M., Gut I., et al. 2013. Divergent transcription is associated with promoters of transcriptional regulators. BMC Genomics. 14, 914.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Hansen T.B., Jensen T., Clausen B.H., Bramsen J.B., Finsen B., Damgaard C.K., Kjems J. 2013. Natural RNA circles function as efficient microRNA sponges. Nature. 495, 384‒388.CrossRefPubMedGoogle Scholar
  45. 45.
    Li J., Yang J., Zhou P., Le Y., Zhou C., Wang S., Xu D., Lin H.K., Gong Z. 2015. Circular RNAs in cancer: Novel insights into origins, properties, functions and implications. Am. J. Cancer Res. 5, 472‒480.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Mercer T.R. 2011. The human mitochondrial transcriptome. Cell. 146, 645‒658.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Jarroux J., Morillon A., Pinskaya M. 2017. History, discovery, and classification of lncRNAs. Adv. Exp. Med. Biol. 1008, 1‒46.CrossRefPubMedGoogle Scholar
  48. 48.
    Ayupe A.C., Tahira A.C., Camargo L., Beckedorff F.C., Verjovski-Almeida S., Reis E.M. 2015. Global analysis of biogenesis, stability and sub-cellular localization of lncRNAs mapping to intragenic regions of the human genome. RNA Biol. 12, 877‒892.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Cabili M.N., Dunagin M.C., McClanahan P.D., Biaesch A., Padovan-Merhar O., Regev A., Rinn J.L., Raj A. 2015. Localization and abundance analysis of human lncRNAs at single-cell and single-molecule resolution. Genome Biol. 16, 20.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Lubas M., Andersen P.R., Schein A., Dziembowski A., Kudla G., Jensen T.H. 2015. The human nuclear exosome targeting complex is loaded onto newly synthesized RNA to direct early ribonucleolysis. Cell Rep. 10, 178‒192.CrossRefPubMedGoogle Scholar
  51. 51.
    Lennox K.A., Behlke M.A. 2016. Cellular localization of long non-coding RNAs affects silencing by RNAi more than by antisense oligonucleotides. Nucleic Acids Res. 44, 863‒877.CrossRefPubMedGoogle Scholar
  52. 52.
    Chen L.L. 2016. Linking long noncoding RNA loca-lization and function. Trends Biochem. Sci. 41, 761‒772.CrossRefPubMedGoogle Scholar
  53. 53.
    Long Y., Wang X., Youmans D.T., Cech T.R. 2017. How do lncRNAs regulate transcription? Sci. Adv. 3, 1‒13.Google Scholar
  54. 54.
    Zhang B., Gunawardane L., Niazi F., Jahanbani F., Chen X., Valadkhan S. 2014. A novel RNA motif mediates the strict nuclear localization of a long noncoding RNA. Mol. Cell Biol. 34, 2318‒2329.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Wickramasinghe V.O., Laskey R.A. 2015. Control of mammalian gene expression by selective mRNA export. Nat. Rev. Mol. Cell. Biol. 16, 431‒442.CrossRefPubMedGoogle Scholar
  56. 56.
    Miyagawa R., Tano K., Mizuno R., Nakamura Y., Ijiri K., Rakwal R., Shibato J., Masuo Y., Mayeda A., Hirose T., Akimitsu N. 2012. Identification of cis- and trans-acting factors involved in the localization of MALAT-1 noncoding RNA to nuclear speckles. RNA. 18, 738‒751.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Jacob M.D., Audas T.E., Uniacke J., Trinkle-Mulcahy L., Lee S. 2013. Environmental cues induce a long noncoding RNA-dependent remodeling of the nucleolus. Mol. Biol. Cell. 24, 2943‒2953.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Anandakumar S., Vijayakumar S., Arumugam N., Gromiha M.M. 2015. Mammalian mitochondrial ncRNA database. Bioinformation. 11, 512‒513.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Cech T.R., Steitz J.A. 2014. The noncoding RNA revolution-trashing old rules to forge new ones. Cell. 157, 77‒94.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Zhang C., Peng G. 2015. Non-coding RNAs: An emerging player in DNA damage response. Mutat. Res. Rev. Mutat. Res. 763, 202‒211.CrossRefPubMedGoogle Scholar
  61. 61.
    Melissari M.T., Grote P. 2016. Roles for long non-coding RNAs in physiology and disease. Pflugers Arch. 468, 945‒958.CrossRefPubMedGoogle Scholar
  62. 62.
    Tsai M.C., Manor O., Wan Y., Mosammaparast N., Wang J.K., Lan F., Shi Y., Segal E., Chang H.Y. 2010. Long noncoding RNA as modular scaffold of histone modification complexes. Science. 329, 689‒693.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Rinn J.L., Kertesz M., Wang J.K., Squazzo S.L., Xu X., Brugmann S.A., Goodnough L.H., Helms J.A., Farnham P.J., Segal E., Chang H.Y. 2007. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 129, 1311‒1323.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Braidotti G., Baubec T., Pauler F., Seidl C., Smrzka O., Stricker S., Yotova I., Barlow D.P. 2004. The Air noncoding RNA: An imprinted cis-silencing transcript. Cold Spring Harb. Symp. Quant. Biol. 69, 55‒66.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Gilbert S.L., Pehrson J.R., Sharp P.A. 2000. XIST RNA associates with specific regions of the inactive X chromatin. J. Biol. Chem. 275, 36491‒36494.CrossRefPubMedGoogle Scholar
  66. 66.
    Golding M.C., Magri L.S., Zhang L., Lalone S.A., Higgins M.J., Mann M.R. 2011. Depletion of Kcnq1ot1 non-coding RNA does not affect imprinting maintenance in stem cells. Development. 138, 3667‒3678.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Karapetyan A.R., Buiting C., Kuiper R.A., Coolen M.W. 2013. Regulatory roles for long ncRNA and mRNA. Cancers (Basel). 5, 462‒490.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Yoon J.H., Abdelmohsen K., Srikantan S., Yang X., Martindale J.L., De S., Huarte M., Zhan M., Becker K.G., Gorospe M. 2012. LincRNA-p21 suppresses target mRNA translation. Mol. Cell. 47, 648‒655.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Clark M.B., Mattick J.S. 2011. Long noncoding RNAs in cell biology. Semin. Cell Dev. Biol. 22, 366‒376.CrossRefPubMedGoogle Scholar
  70. 70.
    Geisler S., Coller J. 2013. RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts. Nat. Rev. Mol. Cell Biol. 14, 699‒712.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Morris K.V., Mattick J.S. 2014. The rise of regulatory RNA. Nat. Rev. Genet. 15, 423‒437.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Ernst C., Morton C.C. 2013. Identification and function of long non-coding RNA. Front. Cell Neurosci. 7, 168.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Zhang Y., Tao Y., Liao Q. 2017. Long noncoding RNA: A crosslink in biological regulatory network. Brief Bioinform. doi 10.1093/bib/bbx042Google Scholar
  74. 74.
    Rinn J.L., Chang H.Y. 2012. Genome regulation by long noncoding RNAs. Annu. Rev. Biochem. 81, 145‒166.CrossRefPubMedGoogle Scholar
  75. 75.
    Wang, Y., Dang Y., Liu J., Ouyang X. 2016. The function of homeobox genes and lncRNAs in cancer. Oncol. Lett. 12, 1635‒1641.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Gupta R.A., Shah N., Wang K.C., Kim J., Horlings H.M., Wong D.J., Tsai M.C., Hung T., Argani P., Rinn J.L., Wang Y., Brzoska P., Kong B., Li R., West R.B., et al. 2010. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 464, 1071‒1076.CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Bhan A., Mandal S.S. 2015. LncRNA HOTAIR: A master regulator of chromatin dynamics and cancer. Biochim. Biophys. Acta. 1856, 151‒164.PubMedPubMedCentralGoogle Scholar
  78. 78.
    Kondo Y., Shinjo K., Katsushima K. 2017. Long non-coding RNAs as an epigenetic regulator in human cancers. Cancer Sci. 108, 1927‒1933.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Lee J.T. 2009. Lessons from X-chromosome inactivation: Long ncRNA as guides and tethers to the epigenome. Genes Dev. 23, 1831‒1842.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Wutz A., Gribnau J. 2007. X inactivation Xplained. Curr. Opin. Genet. Dev. 17, 387‒393.CrossRefPubMedGoogle Scholar
  81. 81.
    Pontier D.B., Gribnau J. 2011. Xist regulation and function explored. Hum. Genet. 130, 223‒236.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Taft R.J., Pang K.C., Mercer T.R., Dinger M., Mattick J.S. 2010. Non-coding RNAs: Regulators of disease. J. Pathol. 220, 126‒139.CrossRefPubMedGoogle Scholar
  83. 83.
    Sarma K., Cifuentes-Rojas C., Ergun A., Del Rosario A., Jeon Y., White F., Sadreyev R., Lee J.T. 2014. ATRX directs binding of PRC2 to Xist RNA and polycomb targets. Cell. 159, 1228.CrossRefPubMedGoogle Scholar
  84. 84.
    Sun S., Del Rosario B.C., Szanto A., Ogawa Y., Jeon Y., Lee J.T. 2013. Jpx RNA activates Xist by evicting CTCF. Cell. 153, 1537‒1551.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Reik W., Murrell A. 2000. Genomic imprinting. Silence across the border. Nature. 405, 408‒409.CrossRefPubMedGoogle Scholar
  86. 86.
    Bolha L., Ravnik-Glavac M., Glavac D. 2017. Long noncoding RNAs as biomarkers in cancer. Dis. Markers. 2017, 7243968.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Nagano T., Mitchell J.A., Sanz L.A., Pauler F.M., Ferguson-Smith A.C., Feil R., Fraser P. 2008. The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science. 322, 1717‒1720.CrossRefPubMedGoogle Scholar
  88. 88.
    Klattenhoff C.A., Scheuermann J.C., Surface L.E., Bradley R.K., Fields P.A., Steinhauser M.L., Ding H., Butty V.L., Torrey L., Haas S., Abo R., Tabebordbar M., Lee R.T., Burge C.B., Boyer L.A. 2013. Braveheart, a long noncoding RNA required for cardiovascular lineage commitment. Cell. 152, 570‒583.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Matkovich S.J., Edwards J.R., Grossenheider T.C., de Guzman Strong C., Dorn G.W. 2014. Epigenetic coordination of embryonic heart transcription by dynamically regulated long noncoding RNAs. Proc. Natl. Acad. Sci. U. S. A. 111, 12264‒12269.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Mohammad F., Mondal T., Guseva N., Pandey G.K., Kanduri C. 2010. Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1. Development. 137, 2493‒2499.CrossRefPubMedGoogle Scholar
  91. 91.
    Cao J. 2014. The functional role of long non-coding RNAs and epigenetics. Biol. Proc. Online. 16, 11.CrossRefGoogle Scholar
  92. 92.
    Arab K., Park Y.J., Lindroth A.M., Schäfer A., Oakes C., Weichenhan D., Lukanova A., Lundin E., Risch A., Meister M., Dienemann H., Dyckhoff G., Herold-Mende C., Grummt I., Niehrs C., Plass C. 2014. Long noncoding RNA TARID directs demethylation and activation of the tumor suppressor TCF21 via GADD45A. Mol. Cell. 55, 604‒614.CrossRefPubMedGoogle Scholar
  93. 93.
    Carlevaro-Fita J., Rahim A., Guigó R., Vardy L.A., Johnson R. 2016. Cytoplasmic long noncoding RNAs are frequently bound to and degraded at ribosomes in human cells. RNA. 22, 867‒882.CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Dey B.K., Pfeifer K., Dutta A. 2014. The H19 long noncoding RNA gives rise to microRNAs miR-675-3p and miR-675-5p to promote skeletal muscle differentiation and regeneration. Genes Dev. 28, 491‒501.CrossRefPubMedPubMedCentralGoogle Scholar
  95. 95.
    Alvarez M.L., Khosroheidari M., Eddy E., Kiefer J. 2013. Role of microRNA 1207-5P and its host gene, the long non-coding RNA Pvt1, as mediators of extracellular matrix accumulation in the kidney: Implications for diabetic nephropathy. PLoS One. 8, 1‒14.Google Scholar
  96. 96.
    Legnini I., Morlando M., Mangiavacchi A., Fatica A., Bozzoni I. 2014. A feedforward regulatory loop between HuR and the long noncoding RNA linc-MD1 controls early phases of myogenesis. Mol. Cell. 53, 506‒514.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Cesana M., Cacchiarelli D., Legnini I., Santini T., Sthandier O., Chinappi M., Tramontano A., Bozzoni I. 2011. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 147, 358‒369.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Xu R., Zhu X., Chen F., Huang C., Ai K., Wu H., Zhang L., Zhao X. 2018. LncRNA XIST/miR-200c regulates the stemness properties and tumourigenicity of human bladder cancer stem cell-like cells. Cancer Cell. Int. 18, 41.CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Esteller M. 2011. Non-coding RNAs in human disease. Nat. Rev. Genet. 12, 861‒874.CrossRefPubMedGoogle Scholar
  100. 100.
    Kwok Z.H., Tay Y. 2017. Long noncoding RNAs: Links between human health and disease. Biochem. Soc. Trans. 45, 805‒812.CrossRefPubMedGoogle Scholar
  101. 101.
    Nie L., Wu H.J., Hsu J.M., Chang S.S., Labaff A.M., Li C.W., Wang Y., Hsu J.L., Hung M.C. 2012. Long non-coding RNAs: Versatile master regulators of gene expression and crucial players in cancer. Am. J. Transl. Res. 4, 127‒150.PubMedPubMedCentralGoogle Scholar
  102. 102.
    Pullen T.J., Rutter G.A. 2014. Roles of lncRNAs in pancreatic beta cell identity and diabetes susceptibility. Front. Genet. 5, 193.CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Soreq L., Guffanti A., Salomonis N., Simchovitz A., Israel Z., Bergman H., Soreq H. 2014. Long non-coding RNA and alternative splicing modulations in Parkinson’s leukocytes identified by RNA sequencing. PLoS Comput. Biol. 10, e1003517.CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Tsoi L.C., Iyer M.K., Stuart P.E., Swindell W.R., Gudjonsson J.E., Tejasvi T., Sarkar M.K., Li B., Ding J., Voorhees J.J., Kang H.M., Nair R.P., Chinnaiyan A.M., Abecasis G.R., Elder J.T. 2015. Analysis of long non-coding RNAs highlights tissue-specific expression patterns and epigenetic profiles in normal and psoriatic skin. Genome Biol. 16, 24.CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Chen G., Wang Z., Wang D., Qiu C., Liu M., Chen X., Zhang Q., Yan G., Cui Q. 2013. LncRNADisease: a database for long-non-coding RNA-associated diseases. Nucleic Acids Res. 41, D983‒D986.CrossRefPubMedGoogle Scholar
  106. 106.
    Bartonicek N., Maag J.L., Dinger M.E. 2016. Long noncoding RNAs in cancer: Mechanisms of action and technological advancements. Mol. Cancer. 15, 43.CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Gutschner T., Hammerle M., Diederichs S. 2013. MALAT1: A paradigm for long noncoding RNA function in cancer. J. Mol. Med. 91, 791‒801.CrossRefPubMedGoogle Scholar
  108. 108.
    Hu X., Feng Y., Zhang D., Zhao S.D., Hu Z., Greshock J., Zhang Y., Yang L., Zhong X., Wang L.P., Jean S., Li C., Huang Q., Katsaros D., Montone K.T., et al. 2014. A functional genomic approach identifies FAL1 as an oncogenic long noncoding RNA that associates with BMI1 and represses p21 expression in cancer. Cancer Cell. 26, 344‒357.CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Lisitsyn N.A., Chernyi A.A., Karpov V.L., Beresten S.F. 2015. A role of long noncoding RNAs in carcinogenesis. Mol. Biol. (Moscow). 49, 500‒507.CrossRefGoogle Scholar
  110. 110.
    Huarte M., Rinn J.L. 2010. Large non-coding RNAs: Missing links in cancer? Hum. Mol. Genet. 19, R152‒161.CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Geng Y.J., Xie S.L., Li Q., Ma J., Wang G.Y. 2011. Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J. Int. Med. Res. 39, 2119‒2128.PubMedGoogle Scholar
  112. 112.
    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, 946‒950.CrossRefPubMedGoogle Scholar
  113. 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, 1616‒1625.CrossRefPubMedGoogle Scholar
  114. 114.
    Li D., Feng J., Wu T., Wang Y., Sun Y., Ren J., Liu M. 2013. Long intergenic noncoding RNA HOTAIR is overexpressed and regulates PTEN methylation in laryngeal squamous cell carcinoma. Am. J. Pathol. 182, 64‒70.CrossRefPubMedGoogle Scholar
  115. 115.
    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, 319‒324.CrossRefPubMedGoogle Scholar
  116. 116.
    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, 6320‒6326.CrossRefPubMedGoogle Scholar
  117. 117.
    Ji P., Diederichs S., Wang W., Böing S., Metzger R., Schneider P.M., Tidow N., Brandt B., Buerger H., Bulk E., Thomas M., Berdel W.E., Serve H., Müller-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, 8031‒8041.CrossRefPubMedGoogle Scholar
  118. 118.
    Tripathi V., Shen Z., Chakraborty A., Giri S., Freier S.M., Wu X., Zhang Y., Gorospe M., Prasanth S.G., Lal A., Prasanth K.V. 2013. Long noncoding RNA MALAT1 controls cell cycle progression by regulating the expression of oncogenic transcription factor B-MYB. PLoS Genet. 9, e1003368.CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Liu J., Peng W.X., Mo Y.Y., Luo D. 2017. MALAT1-mediated tumorigenesis. Front. Biosci. Landmark Ed. 22, 66‒80.CrossRefPubMedGoogle Scholar
  120. 120.
    Zhu L., Liu J., Ma S., Zhang S. 2015. Long noncoding RNA MALAT-1 can predict metastasis and a poor prognosis: A meta-analysis. Pathol. Oncol. Res. 21, 1259‒1264.CrossRefPubMedGoogle Scholar
  121. 121.
    Loewer S., Cabili M.N., Guttman M., Loh Y.H., Thomas K., Park I.H., Garber M., Curran M., Onder T., Agarwal S., Manos P.D., Datta S., Lander E.S., Schlaeger T.M., Daley G.Q., Rinn J.L. 2010. Large intergenic non-coding RNA-RoR modulates reprogramming of human induced pluripotent stem cells. Nat. Genet. 42, 1113‒1117.CrossRefPubMedPubMedCentralGoogle Scholar
  122. 122.
    Zhang A., Zhou N., Huang J., Liu Q., Fukuda K., Ma D., Lu Z., Bai C., Watabe K., Mo Y.Y. 2013. The human long non-coding RNA-RoR is a p53 repressor in response to DNA damage. Cell Res. 23, 340‒350.CrossRefPubMedGoogle Scholar
  123. 123.
    Khurana E., Fu Y., Chakravarty D., Demichelis F., Rubin M.A., Gerstein M. 2016. Role of non-coding sequence variants in cancer. Nat. Rev. Genet. 17, 93‒108.CrossRefPubMedGoogle Scholar
  124. 124.
    Yan X., Hu Z., Feng Y., Hu X., Yuan J., Zhao S.D., Zhang Y., Yang L., Shan W., He Q., Fan L., Kandalaft L.E., Tanyi J.L., Li C., Yuan C.X., et al. 2015. Comprehensive genomic characterization of long non-coding RNAs across human cancers. Cancer Cell. 28, 529‒540.CrossRefPubMedPubMedCentralGoogle Scholar
  125. 125.
    Redis R.S., Vela L.E., Lu W., Ferreira de Oliveira J., Ivan C., Rodriguez-Aguayo C., Adamoski D., Pasculli B., Taguchi A., Chen Y., Fernandez A.F., Valledor L., Van Roosbroeck K., Chang S., Shah M., et al. 2016. Allele-specific reprogramming of cancer metabolism by the long non-coding RNA CCAT2. Mol. Cell. 61, 520‒534.CrossRefPubMedPubMedCentralGoogle Scholar
  126. 126.
    Pandey G.K., Mitra S., Subhash S., Hertwig F., Kanduri M., Mishra K., Fransson S., Ganeshram A., Mondal T., Bandaru S., Ostensson M., Akyürek L.M., Abrahamsson J., Pfeifer S., Larsson E., et al. 2014. The risk-associated long noncoding RNA NBAT-1 controls neuroblastoma progression by regulating cell proliferation and neuronal differentiation. Cancer Cell. 26, 722‒737.CrossRefPubMedGoogle Scholar
  127. 127.
    Yarmishyn A.A., Kurochkin I.V. 2015. Long noncoding RNAs: A potential novel class of cancer biomarkers. Front. Genet. 6, 145.CrossRefPubMedPubMedCentralGoogle Scholar
  128. 128.
    Akers J.C., Gonda D., Kim R., Carter B.S., Chen C.C. 2013. Biogenesis of extracellular vesicles (EV): Exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J. Neurooncol. 113, 1‒11.CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    Shi T., Gao G., Cao Y. 2016. Long noncoding RNAs as novel biomarkers have a promising future in cancer diagnostics. Dis. Markers. 2016, 9085195.CrossRefPubMedPubMedCentralGoogle Scholar
  130. 130.
    Arita T., Ichikawa D., Konishi H., Komatsu S., Shiozaki A., Shoda K., Kawaguchi T., Hirajima S., Nagata H., Kubota T., Fujiwara H., Okamoto K., Otsuji E. 2013. Circulating long non-coding RNAs in plasma of patients with gastric cancer. Anticancer Res. 33, 3185‒3193.PubMedGoogle Scholar
  131. 131.
    Silva A., Bullock M., Calin G. 2015. The clinical relevance of long non-coding RNAs in cancer. Cancers (Basel). 7, 2169‒2182.CrossRefPubMedPubMedCentralGoogle Scholar
  132. 132.
    Li J., Wang X., Tang J., Jiang R., Zhang W., Ji J., Sun B. 2015. HULC and Linc00152 act as novel biomarkers in predicting diagnosis of hepatocellular carcinoma. Cell. Physiol. Biochem. 37, 687‒696.CrossRefPubMedGoogle Scholar
  133. 133.
    Dong L., Qi P., Xu M.D., Ni S.J., Huang D., Xu Q.H., Weng W.W., Tan C., Sheng W.Q., Zhou X.Y., Du X. 2015. Circulating CUDR, LSINCT-5 and PTENP1 long noncoding RNAs in sera distinguish patients with gastric cancer from healthy controls. Int. J. Cancer. 137, 1128‒1135.CrossRefPubMedGoogle Scholar
  134. 134.
    Bourdoumis A., Papatsoris A.G., Chrisofos M., Efstathiou E., Skolarikos A., Deliveliotis C. 2010. The novel prostate cancer antigen 3 (PCA3) biomarker. Int. Braz. J. Urol. 36, 665‒668.CrossRefPubMedGoogle Scholar
  135. 135.
    de Kok J.B., Verhaegh G.W., Roelofs R.W., Hessels D., Kiemeney L.A., Aalders T.W., Swinkels D.W., Schalken J.A. 2002. DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res. 62, 2695‒2698.PubMedGoogle Scholar
  136. 136.
    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, 1919‒1927.CrossRefPubMedGoogle Scholar
  137. 137.
    Rao A., Rajkumar T., Mani S. 2017. Perspectives of long non-coding RNAs in cancer. Mol. Biol. Rep. 44, 203‒218.CrossRefPubMedGoogle Scholar
  138. 138.
    Bhan A., Soleimani M., Mandal S.S. 2017. Long noncoding RNA and cancer: A new paradigm. Cancer Res. 77, 3965‒3981.CrossRefPubMedGoogle Scholar
  139. 139.
    Arun G., Diermeier S., Akerman M., Chang K.C., Wilkinson J.E., Hearn S., Kim Y., MacLeod A.R., Krainer A.R., Norton L., Brogi E., Egeblad M., Spector D.L. 2016. Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss. Genes Dev. 30, 34‒51.CrossRefPubMedPubMedCentralGoogle Scholar
  140. 140.
    Wu Y., Liu J., Zheng Y., You L., Kuang D., Liu T. 2014. Suppressed expression of long non-coding RNA HOTAIR inhibits proliferation and tumourigenicity of renal carcinoma cells. Tumour Biol. 35, 11887‒11894.CrossRefPubMedGoogle Scholar
  141. 141.
    Chen H., Xin Y., Zhou L., Huang J.M., Tao L., Cheng L., Tian J. 2014. Cisplatin and paclitaxel target significant long noncoding RNAs in laryngeal squamous cell carcinoma. Med. Oncol. 31, 246.CrossRefPubMedGoogle Scholar
  142. 142.
    Xue X., Yang Y.A., Zhang A., Fong K.W., Kim J., Song B., Li S., Zhao J.C., Yu J. 2016. LncRNA HOTAIR enhances ER signaling and confers tamoxifen resistance in breast cancer. Oncogene. 35, 2746‒2755.CrossRefPubMedGoogle Scholar
  143. 143.
    Han P., Han L.M., Gao Q., Sun Y. 2017. The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/beta-catenin signaling. Mol. Cancer. 16, 9.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Pleiades Publishing, Inc. 2018

Authors and Affiliations

  • I. V. Bure
    • 1
  • E. B. Kuznetsova
    • 1
    • 2
  • D. V. Zaletaev
    • 1
    • 2
    Email author
  1. 1.Institute of Molecular Medicine, Sechenov First Moscow State Medical University (Sechenov University)MoscowRussia
  2. 2.Research Center for Medical GeneticsMoscowRussia

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