The discovery of long noncoding RNAs (lncRNA) has provided a new perspective on gene regulation in diverse biological contexts. lncRNAs are remarkably versatile molecules that interact with RNA, DNA, or proteins to promote or restrain the expression of protein-coding genes. Activation of immune cells is associated with dynamic changes in expression of genes, the products of which combat infectious microorganisms, initiate repair, and resolve inflammatory responses in cells and tissues. Recent evidence indicates that lncRNAs play important roles in directing the development of diverse immune cells and controlling the dynamic transcriptional programs that are a hallmark of immune cell activation. The importance of these molecules is underscored by their newly recognized roles in inflammatory diseases. In this review, we discuss the contribution of lncRNAs in the development and activation of immune cells and their roles in immune-related diseases. We also discuss challenges faced in identifying biological functions for this large and complex class of genes.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Medzhitov R, Horng T. 1.  2009. Transcriptional control of the inflammatory response. Nat. Rev. Immunol. 9:692–703 [Google Scholar]
  2. Ulitsky I, Bartel DP. 2.  2013. lincRNAs: genomics, evolution, and mechanisms. Cell 154:26–46 [Google Scholar]
  3. Rinn JL, Chang HY. 3.  2012. Genome regulation by long noncoding RNAs. Annu. Rev. Biochem. 81:145–66 [Google Scholar]
  4. Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S. 4.  et al. 2012. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22:1775–89 [Google Scholar]
  5. Harrow J, Frankish A, Gonzalez JM, Tapanari E, Diekhans M. 5.  et al. 2012. GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res 22:1760–74 [Google Scholar]
  6. Werner A, Carlile M, Swan D. 6.  2009. What do natural antisense transcripts regulate?. RNA Biol 6:43–48 [Google Scholar]
  7. Lin MF, Jungreis I, Kellis M. 7.  2011. PhyloCSF: a comparative genomics method to distinguish protein coding and non-coding regions. Bioinformatics 27:i275–82 [Google Scholar]
  8. Kong L, Zhang Y, Ye ZQ, Liu XQ, Zhao SQ. 8.  et al. 2007. CPC: Assess the protein-coding potential of transcripts using sequence features and support vector machine. Nucleic Acids Res 35:W345–49 [Google Scholar]
  9. Guttman M, Russell P, Ingolia NT, Weissman JS, Lander ES. 9.  2013. Ribosome profiling provides evidence that large noncoding RNAs do not encode proteins. Cell 154:240–51 [Google Scholar]
  10. Dinger ME, Pang KC, Mercer TR, Mattick JS. 10.  2008. Differentiating protein-coding and noncoding RNA: challenges and ambiguities. PLOS Comput. Biol. 4:e1000176 [Google Scholar]
  11. Wadler CS, Vanderpool CK. 11.  2007. A dual function for a bacterial small RNA: SgrS performs base pairing-dependent regulation and encodes a functional polypeptide. PNAS 104:20454–59 [Google Scholar]
  12. Morita T, Aiba H. 12.  2007. Small RNAs making a small protein. PNAS 104:20149–50 [Google Scholar]
  13. Washietl S, Kellis M, Garber M. 13.  2014. Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals. Genome Res 24:616–28 [Google Scholar]
  14. Wiberg RA, Halligan DL, Ness RW, Necsulea A, Kaessmann H, Keightley PD. 14.  2015. Assessing recent selection and functionality at long noncoding RNA loci in the mouse genome. Genome Biol. Evol. 7:2432–44 [Google Scholar]
  15. Necsulea A, Soumillon M, Warnefors M, Liechti A, Daish T. 15.  et al. 2014. The evolution of lncRNA repertoires and expression patterns in tetrapods. Nature 505:635–40 [Google Scholar]
  16. Hedges SB. 16.  2002. The origin and evolution of model organisms. Nat. Rev. Genet. 3:838–49 [Google Scholar]
  17. Kapusta A, Kronenberg Z, Lynch VJ, Zhuo X, Ramsay L. 17.  et al. 2013. Transposable elements are major contributors to the origin, diversification, and regulation of vertebrate long noncoding RNAs. PLOS Genet 9:e1003470 [Google Scholar]
  18. Kelley D, Rinn J. 18.  2012. Transposable elements reveal a stem cell-specific class of long noncoding RNAs. Genome Biol 13:R107 [Google Scholar]
  19. Kim EZ, Wespiser AR, Caffrey DR. 19.  2016. The domain structure and distribution of Alu elements in long noncoding RNAs and mRNAs. RNA 22:254–64 [Google Scholar]
  20. Hu W, Alvarez-Dominguez JR, Lodish HF. 20.  2012. Regulation of mammalian cell differentiation by long non-coding RNAs. EMBO Rep 13:971–83 [Google Scholar]
  21. Grote P, Wittler L, Hendrix D, Koch F, Wahrisch S. 21.  et al. 2013. The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Dev. Cell 24:206–14 [Google Scholar]
  22. Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK. 22.  et al. 2011. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 477:295–300 [Google Scholar]
  23. Kretz M, Siprashvili Z, Chu C, Webster DE, Zehnder A. 23.  et al. 2013. Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature 493:231–35 [Google Scholar]
  24. Hu W, Yuan B, Flygare J, Lodish HF. 24.  2011. Long noncoding RNA-mediated anti-apoptotic activity in murine erythroid terminal differentiation. Genes Dev 25:2573–78 [Google Scholar]
  25. Alvarez-Dominguez JR, Hu W, Yuan B, Shi J, Park SS. 25.  et al. 2014. Global discovery of erythroid long noncoding RNAs reveals novel regulators of red cell maturation. Blood 123:570–81 [Google Scholar]
  26. Sun L, Goff LA, Trapnell C, Alexander R, Lo KA. 26.  et al. 2013. Long noncoding RNAs regulate adipogenesis. PNAS 110:3387–92 [Google Scholar]
  27. Zhang X, Lian Z, Padden C, Gerstein MB, Rozowsky J. 27.  et al. 2009. A myelopoiesis-associated regulatory intergenic noncoding RNA transcript within the human HOXA cluster. Blood 113:2526–34 [Google Scholar]
  28. Bei L, Lu Y, Bellis SL, Zhou W, Horvath E, Eklund EA. 28.  2007. Identification of a HoxA10 activation domain necessary for transcription of the gene encoding β3 integrin during myeloid differentiation. J. Biol. Chem. 282:16846–59 [Google Scholar]
  29. Eklund EA. 29.  2006. The role of HOX genes in myeloid leukemogenesis. Curr. Opin. Hematol. 13:67–73 [Google Scholar]
  30. Rice KL, Licht JD. 30.  2007. HOX deregulation in acute myeloid leukemia. J. Clin. Investig. 117:865–68 [Google Scholar]
  31. Kotzin JJ, Spencer SP, McCright SJ, Kumar DB, Collet MA. 31.  et al. 2016. The long non-coding RNA Morrbid regulates Bim and short-lived myeloid cell lifespan. Nature 537:239–43 [Google Scholar]
  32. Wang P, Xue Y, Han Y, Lin L, Wu C. 32.  et al. 2014. The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation. Science 344:310–13 [Google Scholar]
  33. Steinman RM, Hemmi H. 33.  2006. Dendritic cells: translating innate to adaptive immunity. Curr. Top. Microbiol. Immunol. 311:17–58 [Google Scholar]
  34. Schmidt SV, Nino-Castro AC, Schultze JL. 34.  2012. Regulatory dendritic cells: There is more than just immune activation. Front. Immunol. 3:274 [Google Scholar]
  35. Murphy KM. 35.  2013. Transcriptional control of dendritic cell development. Adv. Immunol. 120:239–67 [Google Scholar]
  36. Dijkstra JM, Ballingall KT. 36.  2014. Non-human lnc-DC orthologs encode Wdnm1-like protein. F1000Research 3:160 [Google Scholar]
  37. Hu G, Gong AY, Wang Y, Ma S, Chen X. 37.  et al. 2016. LincRNA-Cox2 promotes late inflammatory gene transcription in macrophages through modulating SWI/SNF-mediated chromatin remodeling. J. Immunol. 196:2799–808 [Google Scholar]
  38. Tong Q, Gong AY, Zhang X, Lin C, Ma S. 38.  et al. 2016. LincRNA-Cox2 modulates TNF-α-induced transcription of Il12b gene in intestinal epithelial cells through regulation of Mi-2/NuRD-mediated epigenetic histone modifications. FASEB J 30:1187–97 [Google Scholar]
  39. Krawczyk M, Emerson BM. 39.  2014. p50-associated COX-2 extragenic RNA (PACER) activates COX-2 gene expression by occluding repressive NF-κB complexes. eLife 3:e01776 [Google Scholar]
  40. Sun S, Del Rosario BC, Szanto A, Ogawa Y, Jeon Y, Lee JT. 40.  2013. Jpx RNA activates Xist by evicting CTCF. Cell 153:1537–51 [Google Scholar]
  41. Rapicavoli NA, Qu K, Zhang J, Mikhail M, Laberge RM, Chang HY. 41.  2013. A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics. eLife 2:e00762 [Google Scholar]
  42. Li Z, Chao TC, Chang KY, Lin N, Patil VS. 42.  et al. 2014. The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL. PNAS 111:1002–7 [Google Scholar]
  43. Hirose T, Virnicchi G, Tanigawa A, Naganuma T, Li R. 43.  et al. 2014. NEAT1 long noncoding RNA regulates transcription via protein sequestration within subnuclear bodies. Mol. Biol. Cell 25:169–83 [Google Scholar]
  44. Clemson CM, Hutchinson JN, Sara SA, Ensminger AW, Fox AH. 44.  et al. 2009. An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol. Cell 33:717–26 [Google Scholar]
  45. Zhang Q, Chen CY, Yedavalli VS, Jeang KT. 45.  2013. NEAT1 long noncoding RNA and paraspeckle bodies modulate HIV-1 posttranscriptional expression. mBio 4:e00596–12 [Google Scholar]
  46. Chan J, Atianand M, Jiang Z, Carpenter S, Aiello D. 46.  et al. 2015. Cutting edge: A natural antisense transcript, AS-α, controls inducible transcription of the proinflammatory cytokine IL-α. J. Immunol. 195:1359–63 [Google Scholar]
  47. IIott NE, Heward JA, Roux B, Tsitsiou E, Fenwick PS. 47.  et al. 2014. Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes. Nat. Commun. 5:3979 Corrigendum. 2015 Nat. Commun. 6:6814 [Google Scholar]
  48. Liu B, Sun L, Liu Q, Gong C, Yao Y. 48.  et al. 2015. A cytoplasmic NF-κB interacting long noncoding RNA blocks IκB phosphorylation and suppresses breast cancer metastasis. Cancer Cell 27:370–81 [Google Scholar]
  49. Atianand MK, Hu W, Satpathy AT, Shen Y, Ricci EP. 49.  et al. 2016. A long noncoding RNA lincRNA-EPS acts as a transcriptional brake to restrain inflammation. Cell 165:1672–85 [Google Scholar]
  50. Buenrostro JD, Giresi PG, Zaba LC, Chang HY, Greenleaf WJ. 50.  2013. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10:1213–18 [Google Scholar]
  51. Schep AN, Buenrostro JD, Denny SK, Schwartz K, Sherlock G, Greenleaf WJ. 51.  2015. Structured nucleosome fingerprints enable high-resolution mapping of chromatin architecture within regulatory regions. Genome Res 25:1757–70 [Google Scholar]
  52. Castellanos-Rubio A, Fernandez-Jimenez N, Kratchmarov R, Luo X, Bhagat G. 52.  et al. 2016. A long noncoding RNA associated with susceptibility to celiac disease. Science 352:91–95 [Google Scholar]
  53. Nakayamada S, Takahashi H, Kanno Y, O'Shea JJ. 53.  2012. Helper T cell diversity and plasticity. Curr. Opin. Immunol. 24:297–302 [Google Scholar]
  54. Ranzani V, Rossetti G, Panzeri I, Arrigoni A, Bonnal RJ. 54.  et al. 2015. The long intergenic noncoding RNA landscape of human lymphocytes highlights the regulation of T cell differentiation by linc-MAF-4. Nat. Immunol. 16:318–25 [Google Scholar]
  55. Ho IC, Lo D, Glimcher LH. 55.  1998. c-maf promotes T helper cell type 2 (Th2) and attenuates Th1 differentiation by both interleukin 4–dependent and –independent mechanisms. J. Exp. Med. 188:1859–66 [Google Scholar]
  56. Sato K, Miyoshi F, Yokota K, Araki Y, Asanuma Y. 56.  et al. 2011. Marked induction of c-Maf protein during Th17 cell differentiation and its implication in memory Th cell development. J. Biol. Chem. 286:14963–71 [Google Scholar]
  57. Miele A, Dekker J. 57.  2009. Mapping cis- and trans- chromatin interaction networks using chromosome conformation capture (3C). Methods Mol. Biol. 464:105–21 [Google Scholar]
  58. Gomez JA, Wapinski OL, Yang YW, Bureau JF, Gopinath S. 58.  et al. 2013. The NeST long ncRNA controls microbial susceptibility and epigenetic activation of the interferon-gamma locus. Cell 152:743–54 [Google Scholar]
  59. Vigneau S, Rohrlich PS, Brahic M, Bureau JF. 59.  2003. Tmevpg1, a candidate gene for the control of Theiler's virus persistence, could be implicated in the regulation of gamma interferon. J. Virol. 77:5632–38 [Google Scholar]
  60. Collier SP, Collins PL, Williams CL, Boothby MR, Aune TM. 60.  2012. Cutting edge: influence of Tmevpg1, a long intergenic noncoding RNA, on the expression of Ifng by Th1 cells. J. Immunol. 189:2084–88 [Google Scholar]
  61. Patel DD, Kuchroo VK. 61.  2015. Th17 Cell pathway in human immunity: lessons from genetics and therapeutic interventions. Immunity 43:1040–51 [Google Scholar]
  62. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A. 62.  et al. 2006. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126:1121–33 [Google Scholar]
  63. Korn T, Bettelli E, Oukka M, Kuchroo VK. 63.  2009. IL-17 and Th17 cells. Annu. Rev. Immunol. 27:485–517 [Google Scholar]
  64. Huang W, Thomas B, Flynn RA, Gavzy SJ, Wu L. 64.  et al. 2015. DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions. Nature 528:517–22 [Google Scholar]
  65. Linder P, Jankowsky E. 65.  2011. From unwinding to clamping—the DEAD box RNA helicase family. Nat. Rev. Mol. Cell Biol. 12:505–16 [Google Scholar]
  66. Martin AN, Li Y. 66.  2007. RNase MRP RNA and human genetic diseases. Cell Res 17:219–26 [Google Scholar]
  67. Willingham AT, Orth AP, Batalov S, Peters EC, Wen BG. 67.  et al. 2005. A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science 309:1570–73 [Google Scholar]
  68. Gorlich D, Kutay U. 68.  1999. Transport between the cell nucleus and the cytoplasm. Annu. Rev. Cell Dev. Biol. 15:607–60 [Google Scholar]
  69. Sharma S, Findlay GM, Bandukwala HS, Oberdoerffer S, Baust B. 69.  et al. 2011. Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex. PNAS 108:11381–86 [Google Scholar]
  70. Liu AY, Torchia BS, Migeon BR, Siliciano RF. 70.  1997. The human NTT gene: identification of a novel 17-kb noncoding nuclear RNA expressed in activated CD4+ T cells. Genomics 39:171–84 [Google Scholar]
  71. Mehta A, Baltimore D. 71.  2016. microRNAs as regulatory elements in immune system logic. Nat. Rev. Immunol. 16:279–94 [Google Scholar]
  72. Brazao TF, Johnson JS, Müller J, Heger A, Ponting CP, Tybulewicz VL. 72.  2016. Long non-coding RNAs in B-cell development and activation. Blood 128:e10–19 [Google Scholar]
  73. Tayari MM, Winkle M, Kortman G, Sietzema J, de Jong D. 73.  et al. 2016. Long noncoding RNA expression profiling in normal B-cell subsets and Hodgkin lymphoma reveals Hodgkin and Reed-Sternberg cell-specific long noncoding RNAs. Am. J. Pathol. 186:2462–72 [Google Scholar]
  74. Bonnal RJ, Ranzani V, Arrigoni A, Curti S, Panzeri I. 74.  et al. 2015. De novo transcriptome profiling of highly purified human lymphocytes primary cells. Sci. Data 2:150051 [Google Scholar]
  75. Sehgal L, Mathur R, Braun FK, Wise JF, Berkova Z. 75.  et al. 2014. FAS-antisense 1 lncRNA and production of soluble versus membrane Fas in B-cell lymphoma. Leukemia 28:2376–87 [Google Scholar]
  76. Rudin CM, Thompson CB. 76.  1997. Apoptosis and disease: regulation and clinical relevance of programmed cell death. Annu. Rev. Med. 48:267–81 [Google Scholar]
  77. Niitsu N, Sasaki K, Umeda M. 77.  1999. A high serum soluble Fas/APO-1 level is associated with a poor outcome of aggressive non-Hodgkin's lymphoma. Leukemia 13:1434–40 [Google Scholar]
  78. Bolland DJ, Wood AL, Johnston CM, Bunting SF, Morgan G. 78.  et al. 2004. Antisense intergenic transcription in V(D)J recombination. Nat. Immunol. 5:630–37 [Google Scholar]
  79. Verma-Gaur J, Torkamani A, Schaffer L, Head SR, Schork NJ, Feeney AJ. 79.  2012. Noncoding transcription within the Igh distal VH region at PAIR elements affects the 3D structure of the Igh locus in pro-B cells. PNAS 109:17004–9 [Google Scholar]
  80. Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T. 80.  2000. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102:553–63 [Google Scholar]
  81. Pefanis E, Wang J, Rothschild G, Lim J, Kazadi D. 81.  et al. 2015. RNA exosome-regulated long non-coding RNA transcription controls super-enhancer activity. Cell 161:774–89 [Google Scholar]
  82. Ouyang J, Zhu X, Chen Y, Wei H, Chen Q. 82.  et al. 2014. NRAV, a long noncoding RNA, modulates antiviral responses through suppression of interferon-stimulated gene transcription. Cell Host Microbe 16:616–26 [Google Scholar]
  83. Peng X, Gralinski L, Armour CD, Ferris MT, Thomas MJ. 83.  et al. 2010. Unique signatures of long noncoding RNA expression in response to virus infection and altered innate immune signaling. mBio 1:e00206–10 [Google Scholar]
  84. Scaria V, Pasha A. 84.  2012. Long non-noding RNAs in infection biology. Front. Genet. 3:308 [Google Scholar]
  85. Cazalla D, Steitz JA. 85.  2010. Down-regulation of a host microRNA by a viral noncoding RNA. Cold Spring Harb. Symp. Quant. Biol. 75:321–24 [Google Scholar]
  86. Saayman S, Ackley A, Turner AM, Famiglietti M, Bosque A. 86.  et al. 2014. An HIV-encoded antisense long noncoding RNA epigenetically regulates viral transcription. Mol. Ther. 221164–75
  87. Broadbent KM, Park D, Wolf AR, Van Tyne D, Sims JS. 87.  et al. 2011. A global transcriptional analysis of Plasmodium falciparum malaria reveals a novel family of telomere-associated lncRNAs. Genome Biol 12:R56 [Google Scholar]
  88. Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O. 88.  et al. 2011. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147:358–69 [Google Scholar]
  89. Carrieri C, Cimatti L, Biagioli M, Beugnet A, Zucchelli S. 89.  et al. 2012. Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature 491:454–57 [Google Scholar]
  90. Yoon JH, Abdelmohsen K, Srikantan S, Yang X, Martindale JL. 90.  et al. 2012. LincRNA-p21 suppresses target mRNA translation. Mol. Cell 47:648–55 [Google Scholar]
  91. Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK. 91.  et al. 2010. Long noncoding RNA as modular scaffold of histone modification complexes. Science 329:689–93 [Google Scholar]
  92. Gupta RA, Shah N, Wang KC, Kim J, Horlings HM. 92.  et al. 2010. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464:1071–76 [Google Scholar]
  93. Chu C, Qu K, Zhong FL, Artandi SE, Chang HY. 93.  2011. Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol. Cell 44:667–78 [Google Scholar]
  94. Chu C, Zhang QC, da Rocha ST, Flynn RA, Bharadwaj M. 94.  et al. 2015. Systematic discovery of Xist RNA binding proteins. Cell 161:404–16 [Google Scholar]
  95. Engreitz JM, Pandya-Jones A, McDonel P, Shishkin A, Sirokman K. 95.  et al. 2013. The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science 341:1237973 [Google Scholar]
  96. Engreitz JM, Sirokman K, McDonel P, Shishkin AA, Surka C. 96.  et al. 2014. RNA-RNA interactions enable specific targeting of noncoding RNAs to nascent pre-mRNAs and chromatin sites. Cell 159:188–99 [Google Scholar]
  97. McHugh CA, Chen CK, Chow A, Surka CF, Tran C. 97.  et al. 2015. The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3. Nature 521:232–36 [Google Scholar]
  98. Simon MD, Wang CI, Kharchenko PV, West JA, Chapman BA. 98.  et al. 2011. The genomic binding sites of a noncoding RNA. PNAS 108:20497–502 [Google Scholar]
  99. Simon MD, Pinter SF, Fang R, Sarma K, Rutenberg-Schoenberg M. 99.  et al. 2013. High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation. Nature 504:465–69 [Google Scholar]
  100. Consortium EP, Bernstein BE, Birney E, Dunham I, Green ED. 100.  et al. 2012. An integrated encyclopedia of DNA elements in the human genome. Nature 489:57–74 [Google Scholar]
  101. Ricano-Ponce I, Wijmenga C. 101.  2013. Mapping of immune-mediated disease genes. Annu. Rev. Genom. Hum. Genet. 14:325–53 [Google Scholar]
  102. Kumar V, Westra HJ, Karjalainen J, Zhernakova DV, Esko T. 102.  et al. 2013. Human disease-associated genetic variation impacts large intergenic non-coding RNA expression. PLOS Genet 9:e1003201 [Google Scholar]
  103. Trimarchi T, Bilal E, Ntziachristos P, Fabbri G, Dalla-Favera R. 103.  et al. 2014. Genome-wide mapping and characterization of Notch-regulated long noncoding RNAs in acute leukemia. Cell 158:593–606 [Google Scholar]
  104. Medyouf H, Gusscott S, Wang H, Tseng JC, Wai C. 104.  et al. 2011. High-level IGF1R expression is required for leukemia-initiating cell activity in T-ALL and is supported by Notch signaling. J. Exp. Med. 208:1809–22 [Google Scholar]
  105. Yildirim E, Kirby JE, Brown DE, Mercier FE, Sadreyev RI. 105.  et al. 2013. Xist RNA is a potent suppressor of hematologic cancer in mice. Cell 152:727–42 [Google Scholar]
  106. Pageau GJ, Hall LL, Ganesan S, Livingston DM, Lawrence JB. 106.  2007. The disappearing Barr body in breast and ovarian cancers. Nat. Rev. Cancer 7:628–33 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error