MicroRNAs, Long Noncoding RNAs, and Their Functions in Human Disease

  • Min Xue
  • Ying Zhuo
  • Bin ShanEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1617)


Majority of the human genome is transcribed into RNAs with absent or limited protein-coding potential. microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are two major families of the non-protein-coding transcripts. miRNAs and lncRNAs can regulate fundamental cellular processes via diverse mechanisms. The expression and function of miRNAs and lncRNAs are tightly regulated in development and physiological homeostasis. Dysregulation of miRNAs and lncRNAs is critical to pathogenesis of human disease. Moreover, recent evidence indicates a cross talk between miRNAs and lncRNAs. Herein we review recent advances in the biology of miRNAs and lncRNAs with respect to the above aspects. We focus on their roles in cancer, respiratory disease, and neurodegenerative disease. The complexity, flexibility, and versatility of the structures and functions of miRNAs and lncRNAs demand integration of experimental and bioinformatics tools to acquire sufficient knowledge for applications of these noncoding RNAs in clinical care.

Key words

MicroRNA Long noncoding RNA 


  1. 1.
    Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S et al (2012) The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22:1775–1789PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297CrossRefPubMedGoogle Scholar
  3. 3.
    Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854CrossRefPubMedGoogle Scholar
  4. 4.
    Kozomara A, Griffiths-Jones S (2014) miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 42:D68–D73CrossRefPubMedGoogle Scholar
  5. 5.
    Lee Y, Kim M, Han J, Yeom KH, Lee S et al (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23:4051–4060PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Bortolin-Cavaille ML, Dance M, Weber M, Cavaille J (2009) C19MC microRNAs are processed from introns of large Pol-II, non-protein-coding transcripts. Nucleic Acids Res 37:3464–3473PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Katahira J, Yoneda Y (2011) Nucleocytoplasmic transport of microRNAs and related small RNAs. Traffic 12:1468–1474CrossRefPubMedGoogle Scholar
  8. 8.
    Bhayani MK, Calin GA, Lai SY (2012) Functional relevance of miRNA sequences in human disease. Mutat Res 731:14–19CrossRefPubMedGoogle Scholar
  9. 9.
    Roberts TC (2014) The MicroRNA biology of the mammalian nucleus. Mol Ther Nucleic Acids 3:e188PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Hu G, Drescher KM, Chen XM (2012) Exosomal miRNAs: biological properties and therapeutic potential. Front Genet 3:56PubMedCentralPubMedGoogle Scholar
  11. 11.
    Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ et al (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659CrossRefPubMedGoogle Scholar
  12. 12.
    Laulagnier K, Motta C, Hamdi S, Roy S, Fauvelle F et al (2004) Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization. Biochem J 380:161–171PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Hogan MC, Manganelli L, Woollard JR, Masyuk AI, Masyuk TV et al (2009) Characterization of PKD protein-positive exosome-like vesicles. J Am Soc Nephrol 20:278–288PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Zhou R, O'Hara SP, Chen XM (2011) MicroRNA regulation of innate immune responses in epithelial cells. Cell Mol Immunol 8:371–379PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Vlassov AV, Magdaleno S, Setterquist R, Conrad R (2012) Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 1820:940–948CrossRefPubMedGoogle Scholar
  16. 16.
    Mittelbrunn M, Gutierrez-Vazquez C, Villarroya-Beltri C, Gonzalez S, Sanchez-Cabo F et al (2011) Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat Commun 2:282PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    McDonald MK, Tian Y, Qureshi RA, Gormley M, Ertel A et al (2014) Functional significance of macrophage-derived exosomes in inflammation and pain. Pain 155:1527–1539PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Putz U, Howitt J, Doan A, Goh CP, Low LH et al (2012) The tumor suppressor PTEN is exported in exosomes and has phosphatase activity in recipient cells. Sci Signal 5:ra70CrossRefPubMedGoogle Scholar
  19. 19.
    Bracken CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J et al (2008) A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res 68:7846–7854CrossRefPubMedGoogle Scholar
  20. 20.
    Li C, Nguyen HT, Zhuang Y, Lin Y, Flemington EK et al (2011) Post-transcriptional up-regulation of miR-21 by type I collagen. Mol Carcinog 50:563–570CrossRefPubMedGoogle Scholar
  21. 21.
    Olsen PH, Ambros V (1999) The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol 216:671–680CrossRefPubMedGoogle Scholar
  22. 22.
    Friedman RC, Farh KK, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19:92–105PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Agarwal V, Bell GW, Nam JW, Bartel DP (2015) Predicting effective microRNA target sites in mammalian mRNAs. eLife 4:e05005PubMedCentralCrossRefGoogle Scholar
  24. 24.
    Maroney PA, Yu Y, Fisher J, Nilsen TW (2006) Evidence that microRNAs are associated with translating messenger RNAs in human cells. Nat Struct Mol Biol 13:1102–1107CrossRefPubMedGoogle Scholar
  25. 25.
    Nottrott S, Simard MJ, Richter JD (2006) Human let-7a miRNA blocks protein production on actively translating polyribosomes. Nat Struct Mol Biol 13:1108–1114CrossRefPubMedGoogle Scholar
  26. 26.
    Petersen CP, Bordeleau ME, Pelletier J, Sharp PA (2006) Short RNAs repress translation after initiation in mammalian cells. Mol Cell 21:533–542CrossRefPubMedGoogle Scholar
  27. 27.
    Pillai RS, Bhattacharyya SN, Artus CG, Zoller T, Cougot N et al (2005) Inhibition of translational initiation by Let-7 MicroRNA in human cells. Science 309:1573–1576CrossRefPubMedGoogle Scholar
  28. 28.
    Humphreys DT, Westman BJ, Martin DI, Preiss T (2005) MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function. Proc Natl Acad Sci U S A 102:16961–16966PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Rehwinkel J, Behm-Ansmant I, Gatfield D, Izaurralde E (2005) A crucial role for GW182 and the DCP1:DCP2 decapping complex in miRNA-mediated gene silencing. RNA 11:1640–1647PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Behm-Ansmant I, Rehwinkel J, Doerks T, Stark A, Bork P et al (2006) mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes. Genes Dev 20:1885–1898PubMedCentralCrossRefPubMedGoogle Scholar
  31. 31.
    Wu L, Fan J, Belasco JG (2006) MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci U S A 103:4034–4039PubMedCentralCrossRefPubMedGoogle Scholar
  32. 32.
    Guo H, Ingolia NT, Weissman JS, Bartel DP (2010) Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466:835–840PubMedCentralCrossRefPubMedGoogle Scholar
  33. 33.
    Liu Z, Liu H, Desai S, Schmitt DC, Zhou M et al (2013) miR-125b functions as a key mediator for snail-induced stem cell propagation and chemoresistance. J Biol Chem 288:4334–4345CrossRefPubMedGoogle Scholar
  34. 34.
    Zhou M, Liu Z, Zhao Y, Ding Y, Liu H et al (2010) MicroRNA-125b confers the resistance of breast cancer cells to paclitaxel through suppression of pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) expression. J Biol Chem 285:21496–21507PubMedCentralCrossRefPubMedGoogle Scholar
  35. 35.
    Kiriakidou M, Tan GS, Lamprinaki S, De Planell-Saguer M, Nelson PT et al (2007) An mRNA m7G cap binding-like motif within human Ago2 represses translation. Cell 129:1141–1151CrossRefPubMedGoogle Scholar
  36. 36.
    Stefani G, Slack FJ (2008) Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol 9:219–230CrossRefPubMedGoogle Scholar
  37. 37.
    Kim DH, Saetrom P, Snove O Jr, Rossi JJ (2008) MicroRNA-directed transcriptional gene silencing in mammalian cells. Proc Natl Acad Sci U S A 105:16230–16235PubMedCentralCrossRefPubMedGoogle Scholar
  38. 38.
    Benhamed M, Herbig U, Ye T, Dejean A, Bischof O (2012) Senescence is an endogenous trigger for microRNA-directed transcriptional gene silencing in human cells. Nat Cell Biol 14:266–275PubMedCentralCrossRefPubMedGoogle Scholar
  39. 39.
    Zardo G, Ciolfi A, Vian L, Starnes LM, Billi M et al (2012) Polycombs and microRNA-223 regulate human granulopoiesis by transcriptional control of target gene expression. Blood 119:4034–4046CrossRefPubMedGoogle Scholar
  40. 40.
    Adilakshmi T, Sudol I, Tapinos N (2012) Combinatorial action of miRNAs regulates transcriptional and post-transcriptional gene silencing following in vivo PNS injury. PLoS One 7:e39674PubMedCentralCrossRefPubMedGoogle Scholar
  41. 41.
    Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R (2008) MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci U S A 105:1608–1613PubMedCentralCrossRefPubMedGoogle Scholar
  42. 42.
    Shimakami T, Yamane D, Jangra RK, Kempf BJ, Spaniel C et al (2012) Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex. Proc Natl Acad Sci U S A 109:941–946PubMedCentralCrossRefPubMedGoogle Scholar
  43. 43.
    Ha TY (2011) The role of MicroRNAs in regulatory T cells and in the immune response. Immune Netw 11:11–41PubMedCentralCrossRefPubMedGoogle Scholar
  44. 44.
    Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S et al (2002) Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99:15524–15529PubMedCentralCrossRefPubMedGoogle Scholar
  45. 45.
    Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674CrossRefPubMedGoogle Scholar
  46. 46.
    He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D et al (2005) A microRNA polycistron as a potential human oncogene. Nature 435:828–833PubMedCentralCrossRefPubMedGoogle Scholar
  47. 47.
    Hayashita Y, Osada H, Tatematsu Y, Yamada H, Yanagisawa K et al (2005) A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 65:9628–9632CrossRefPubMedGoogle Scholar
  48. 48.
    Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H et al (2004) Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64:3753–3756CrossRefPubMedGoogle Scholar
  49. 49.
    Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R et al (2005) RAS is regulated by the let-7 microRNA family. Cell 120:635–647CrossRefPubMedGoogle Scholar
  50. 50.
    Tsang WP, Ng EK, Ng SS, Jin H, Yu J et al (2010) Oncofetal H19-derived miR-675 regulates tumor suppressor RB in human colorectal cancer. Carcinogenesis 31:350–358CrossRefPubMedGoogle Scholar
  51. 51.
    Ueda R, Kohanbash G, Sasaki K, Fujita M, Zhu X et al (2009) Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1. Proc Natl Acad Sci U S A 106:10746–10751PubMedCentralCrossRefPubMedGoogle Scholar
  52. 52.
    Tazawa H, Tsuchiya N, Izumiya M, Nakagama H (2007) Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci U S A 104:15472–15477PubMedCentralCrossRefPubMedGoogle Scholar
  53. 53.
    O'Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D (2007) MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci U S A 104:1604–1609PubMedCentralCrossRefPubMedGoogle Scholar
  54. 54.
    Gironella M, Seux M, Xie MJ, Cano C, Tomasini R et al (2007) Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development. Proc Natl Acad Sci U S A 104:16170–16175PubMedCentralCrossRefPubMedGoogle Scholar
  55. 55.
    Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A et al (2008) The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol 10:593–601CrossRefPubMedGoogle Scholar
  56. 56.
    Nguyen HT, Li C, Lin Z, Zhuang Y, Flemington EK et al (2012) The microRNA expression associated with morphogenesis of breast cancer cells in three-dimensional organotypic culture. Oncol Rep 28:117–126PubMedCentralPubMedGoogle Scholar
  57. 57.
    Wurdinger T, Tannous BA, Saydam O, Skog J, Grau S et al (2008) miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer Cell 14:382–393PubMedCentralCrossRefPubMedGoogle Scholar
  58. 58.
    Lal A, Pan Y, Navarro F, Dykxhoorn DM, Moreau L et al (2009) miR-24-mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cells. Nat Struct Mol Biol 16:492–498PubMedCentralCrossRefPubMedGoogle Scholar
  59. 59.
    Calin GA, Liu CG, Sevignani C, Ferracin M, Felli N et al (2004) MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A 101:11755–11760PubMedCentralCrossRefPubMedGoogle Scholar
  60. 60.
    Chan JA, Krichevsky AM, Kosik KS (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65:6029–6033CrossRefPubMedGoogle Scholar
  61. 61.
    Doghman M, El Wakil A, Cardinaud B, Thomas E, Wang J et al (2010) Regulation of insulin-like growth factor-mammalian target of rapamycin signaling by microRNA in childhood adrenocortical tumors. Cancer Res 70:4666–4675PubMedCentralCrossRefPubMedGoogle Scholar
  62. 62.
    Ma L, Teruya-Feldstein J, Weinberg RA (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449:682–688CrossRefPubMedGoogle Scholar
  63. 63.
    Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E et al (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 101:2999–3004PubMedCentralCrossRefPubMedGoogle Scholar
  64. 64.
    Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR et al (2008) Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci U S A 105:7269–7274PubMedCentralCrossRefPubMedGoogle Scholar
  65. 65.
    Lee YS, Dutta A (2007) The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev 21:1025–1030PubMedCentralCrossRefPubMedGoogle Scholar
  66. 66.
    Mayr C, Hemann MT, Bartel DP (2007) Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science 315:1576–1579PubMedCentralCrossRefPubMedGoogle Scholar
  67. 67.
    Chin LJ, Ratner E, Leng S, Zhai R, Nallur S et al (2008) A SNP in a let-7 microRNA complementary site in the KRAS 3′ untranslated region increases non-small cell lung cancer risk. Cancer Res 68:8535–8540PubMedCentralCrossRefPubMedGoogle Scholar
  68. 68.
    Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A et al (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 103:2257–2261PubMedCentralCrossRefPubMedGoogle Scholar
  69. 69.
    O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT (2005) c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435:839–843CrossRefPubMedGoogle Scholar
  70. 70.
    Peter ME (2009) Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle 8:843–852PubMedCentralCrossRefPubMedGoogle Scholar
  71. 71.
    Li C, Nguyen HT, Zhuang Y, Lin Z, Flemington EK et al (2012) Comparative profiling of miRNA expression of lung adenocarcinoma cells in two-dimensional and three-dimensional cultures. Gene 511:143–150PubMedCentralCrossRefPubMedGoogle Scholar
  72. 72.
    Mouw JK, Yui Y, Damiano L, Bainer RO, Lakins JN et al (2014) Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression. Nat Med 20:360–367PubMedCentralCrossRefPubMedGoogle Scholar
  73. 73.
    Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH et al (2010) The microRNA spectrum in 12 body fluids. Clin Chem 56:1733–1741PubMedCentralCrossRefPubMedGoogle Scholar
  74. 74.
    Taylor DD, Gercel-Taylor C (2008) MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 110:13–21CrossRefPubMedGoogle Scholar
  75. 75.
    Skog J, Wurdinger T, van Rijn S, Meijer DH, Gainche L et al (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10:1470–1476PubMedCentralCrossRefPubMedGoogle Scholar
  76. 76.
    Ng EK, Chong WW, Jin H, Lam EK, Shin VY et al (2009) Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut 58:1375–1381CrossRefPubMedGoogle Scholar
  77. 77.
    Huang Z, Huang D, Ni S, Peng Z, Sheng W et al (2010) Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer 127:118–126CrossRefPubMedGoogle Scholar
  78. 78.
    Pu XX, Huang GL, Guo HQ, Guo CC, Li H et al (2010) Circulating miR-221 directly amplified from plasma is a potential diagnostic and prognostic marker of colorectal cancer and is correlated with p53 expression. J Gastroenterol Hepatol 25:1674–1680CrossRefPubMedGoogle Scholar
  79. 79.
    Cheng H, Zhang L, Cogdell DE, Zheng H, Schetter AJ et al (2011) Circulating plasma MiR-141 is a novel biomarker for metastatic colon cancer and predicts poor prognosis. PLoS One 6:e17745PubMedCentralCrossRefPubMedGoogle Scholar
  80. 80.
    Toiyama Y, Takahashi M, Hur K, Nagasaka T, Tanaka K et al (2013) Serum miR-21 as a diagnostic and prognostic biomarker in colorectal cancer. J Natl Cancer Inst 105:849–859PubMedCentralCrossRefPubMedGoogle Scholar
  81. 81.
    Ogata-Kawata H, Izumiya M, Kurioka D, Honma Y, Yamada Y et al (2014) Circulating exosomal microRNAs as biomarkers of colon cancer. PLoS One 9:e92921PubMedCentralCrossRefPubMedGoogle Scholar
  82. 82.
    Lowery AJ, Miller N, Devaney A, McNeill RE, Davoren PA et al (2009) MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res 11:R27PubMedCentralCrossRefPubMedGoogle Scholar
  83. 83.
    Volinia S, Galasso M, Sana ME, Wise TF, Palatini J et al (2012) Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA. Proc Natl Acad Sci U S A 109:3024–3029PubMedCentralCrossRefPubMedGoogle Scholar
  84. 84.
    Foekens JA, Sieuwerts AM, Smid M, Look MP, de Weerd V et al (2008) Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer. Proc Natl Acad Sci U S A 105:13021–13026PubMedCentralCrossRefPubMedGoogle Scholar
  85. 85.
    Rodriguez-Gonzalez FG, Sieuwerts AM, Smid M, Look MP, Meijer-van Gelder ME et al (2011) MicroRNA-30c expression level is an independent predictor of clinical benefit of endocrine therapy in advanced estrogen receptor positive breast cancer. Breast Cancer Res Treat 127:43–51CrossRefPubMedGoogle Scholar
  86. 86.
    Maillot G, Lacroix-Triki M, Pierredon S, Gratadou L, Schmidt S et al (2009) Widespread estrogen-dependent repression of microRNAs involved in breast tumor cell growth. Cancer Res 69:8332–8340CrossRefPubMedGoogle Scholar
  87. 87.
    Ichikawa T, Sato F, Terasawa K, Tsuchiya S, Toi M et al (2012) Trastuzumab produces therapeutic actions by upregulating miR-26a and miR-30b in breast cancer cells. PLoS One 7:e31422PubMedCentralCrossRefPubMedGoogle Scholar
  88. 88.
    Ebert MS, Neilson JR, Sharp PA (2007) MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 4:721–726CrossRefPubMedGoogle Scholar
  89. 89.
    Ma L, Young J, Prabhala H, Pan E, Mestdagh P et al (2010) miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol 12:247–256PubMedCentralPubMedGoogle Scholar
  90. 90.
    Huang S, Chen Y, Wu W, Ouyang N, Chen J et al (2013) miR-150 promotes human breast cancer growth and malignant behavior by targeting the pro-apoptotic purinergic P2X7 receptor. PLoS One 8:e80707PubMedCentralCrossRefPubMedGoogle Scholar
  91. 91.
    Kuss AW, Chen W (2008) MicroRNAs in brain function and disease. Curr Neurol Neurosci Rep 8:190–197CrossRefPubMedGoogle Scholar
  92. 92.
    Kim J, Inoue K, Ishii J, Vanti WB, Voronov SV et al (2007) A MicroRNA feedback circuit in midbrain dopamine neurons. Science 317:1220–1224PubMedCentralCrossRefPubMedGoogle Scholar
  93. 93.
    Gehrke S, Imai Y, Sokol N, Lu B (2010) Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Nature 466:637–641PubMedCentralCrossRefPubMedGoogle Scholar
  94. 94.
    Blennow K, de Leon MJ, Zetterberg H (2006) Alzheimer’s disease. Lancet 368:387–403CrossRefPubMedGoogle Scholar
  95. 95.
    Cogswell JP, Ward J, Taylor IA, Waters M, Shi Y et al (2008) Identification of miRNA changes in Alzheimer's disease brain and CSF yields putative biomarkers and insights into disease pathways. J Alzheimers Dis 14:27–41CrossRefPubMedGoogle Scholar
  96. 96.
    Maes OC, Chertkow HM, Wang E, Schipper HM (2009) MicroRNA: implications for Alzheimer disease and other human CNS disorders. Curr Genomics 10:154–168PubMedCentralCrossRefPubMedGoogle Scholar
  97. 97.
    Maes OC, Xu S, Yu B, Chertkow HM, Wang E et al (2007) Transcriptional profiling of Alzheimer blood mononuclear cells by microarray. Neurobiol Aging 28:1795–1809CrossRefPubMedGoogle Scholar
  98. 98.
    Blalock EM, Chen KC, Stromberg AJ, Norris CM, Kadish I et al (2005) Harnessing the power of gene microarrays for the study of brain aging and Alzheimer’s disease: statistical reliability and functional correlation. Ageing Res Rev 4:481–512CrossRefPubMedGoogle Scholar
  99. 99.
    Nunez-Iglesias J, Liu CC, Morgan TE, Finch CE, Zhou XJ (2010) Joint genome-wide profiling of miRNA and mRNA expression in Alzheimer's disease cortex reveals altered miRNA regulation. PLoS One 5:e8898PubMedCentralCrossRefPubMedGoogle Scholar
  100. 100.
    Hebert SS, Horre K, Nicolai L, Papadopoulou AS, Mandemakers W et al (2008) Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer’s disease correlates with increased BACE1/beta-secretase expression. Proc Natl Acad Sci U S A 105:6415–6420PubMedCentralCrossRefPubMedGoogle Scholar
  101. 101.
    Hebert SS, Horre K, Nicolai L, Bergmans B, Papadopoulou AS et al (2009) MicroRNA regulation of Alzheimer’s Amyloid precursor protein expression. Neurobiol Dis 33:422–428CrossRefPubMedGoogle Scholar
  102. 102.
    Booton R, Lindsay MA (2014) Emerging role of MicroRNAs and long noncoding RNAs in respiratory disease. Chest 146:193–204CrossRefPubMedGoogle Scholar
  103. 103.
    Williams AE, Moschos SA, Perry MM, Barnes PJ, Lindsay MA (2007) Maternally imprinted microRNAs are differentially expressed during mouse and human lung development. Dev Dyn 236:572–580PubMedCentralCrossRefPubMedGoogle Scholar
  104. 104.
    Harris KS, Zhang Z, McManus MT, Harfe BD, Sun X (2006) Dicer function is essential for lung epithelium morphogenesis. Proc Natl Acad Sci U S A 103:2208–2213PubMedCentralCrossRefPubMedGoogle Scholar
  105. 105.
    Lu Y, Thomson JM, Wong HY, Hammond SM, Hogan BL (2007) Transgenic over-expression of the microRNA miR-17-92 cluster promotes proliferation and inhibits differentiation of lung epithelial progenitor cells. Dev Biol 310:442–453PubMedCentralCrossRefPubMedGoogle Scholar
  106. 106.
    Jardim MJ, Dailey L, Silbajoris R, Diaz-Sanchez D (2012) Distinct microRNA expression in human airway cells of asthmatic donors identifies a novel asthma-associated gene. Am J Respir Cell Mol Biol 47:536–542CrossRefPubMedGoogle Scholar
  107. 107.
    Solberg OD, Ostrin EJ, Love MI, Peng JC, Bhakta NR et al (2012) Airway epithelial miRNA expression is altered in asthma. Am J Respir Crit Care Med 186:965–974PubMedCentralCrossRefPubMedGoogle Scholar
  108. 108.
    Tsitsiou E, Williams AE, Moschos SA, Patel K, Rossios C et al (2012) Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma. J Allergy Clin Immunol 129:95–103CrossRefPubMedGoogle Scholar
  109. 109.
    O'Connell RM, Rao DS, Baltimore D (2012) microRNA regulation of inflammatory responses. Annu Rev Immunol 30:295–312CrossRefPubMedGoogle Scholar
  110. 110.
    Pandit KV, Corcoran D, Yousef H, Yarlagadda M, Tzouvelekis A et al (2010) Inhibition and role of let-7d in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 182:220–229PubMedCentralCrossRefPubMedGoogle Scholar
  111. 111.
    Dakhlallah D, Batte K, Wang Y, Cantemir-Stone CZ, Yan P et al (2013) Epigenetic regulation of miR-17~92 contributes to the pathogenesis of pulmonary fibrosis. Am J Respir Crit Care Med 187:397–405PubMedCentralCrossRefPubMedGoogle Scholar
  112. 112.
    Liu G, Friggeri A, Yang Y, Milosevic J, Ding Q et al (2010) miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis. J Exp Med 207:1589–1597PubMedCentralCrossRefPubMedGoogle Scholar
  113. 113.
    Cushing L, Kuang PP, Qian J, Shao F, Wu J et al (2011) miR-29 is a major regulator of genes associated with pulmonary fibrosis. Am J Respir Cell Mol Biol 45:287–294CrossRefPubMedGoogle Scholar
  114. 114.
    Yang S, Banerjee S, de Freitas A, Sanders YY, Ding Q et al (2012) Participation of miR-200 in pulmonary fibrosis. Am J Pathol 180:484–493PubMedCentralCrossRefPubMedGoogle Scholar
  115. 115.
    Jiang X, Tsitsiou E, Herrick SE, Lindsay MA (2010) MicroRNAs and the regulation of fibrosis. FEBS J 277:2015–2021PubMedCentralCrossRefPubMedGoogle Scholar
  116. 116.
    Ezzie ME, Crawford M, Cho JH, Orellana R, Zhang S et al (2012) Gene expression networks in COPD: microRNA and mRNA regulation. Thorax 67:122–131CrossRefPubMedGoogle Scholar
  117. 117.
    Sato T, Liu X, Nelson A, Nakanishi M, Kanaji N et al (2010) Reduced miR-146a increases prostaglandin E(2)in chronic obstructive pulmonary disease fibroblasts. Am J Respir Crit Care Med 182:1020–1029PubMedCentralCrossRefPubMedGoogle Scholar
  118. 118.
    Lewis A, Riddoch-Contreras J, Natanek SA, Donaldson A, Man WD et al (2012) Downregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD. Thorax 67:26–34CrossRefPubMedGoogle Scholar
  119. 119.
    Cunningham F, Amode MR, Barrell D, Beal K, Billis K et al (2015) Ensembl 2015. Nucleic Acids Res 43:D662–D669CrossRefPubMedGoogle Scholar
  120. 120.
    Lanz RB, McKenna NJ, Onate SA, Albrecht U, Wong J et al (1999) A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell 97:17–27CrossRefPubMedGoogle Scholar
  121. 121.
    Rinn JL, Chang HY (2012) Genome regulation by long noncoding RNAs. Annu Rev Biochem 81:145–166CrossRefPubMedGoogle Scholar
  122. 122.
    Shibayama Y, Fanucchi S, Magagula L, Mhlanga MM (2014) lncRNA and gene looping: what’s the connection? Transcription 5:e28658PubMedCentralCrossRefPubMedGoogle Scholar
  123. 123.
    Shi X, Sun M, Liu H, Yao Y, Song Y (2013) Long non-coding RNAs: a new frontier in the study of human diseases. Cancer Lett 339:159–166CrossRefPubMedGoogle Scholar
  124. 124.
    Zong X, Tripathi V, Prasanth KV (2011) RNA splicing control: yet another gene regulatory role for long nuclear noncoding RNAs. RNA Biol 8:968–977PubMedCentralCrossRefPubMedGoogle Scholar
  125. 125.
    Kretz M, Siprashvili Z, Chu C, Webster DE, Zehnder A et al (2013) Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature 493:231–235CrossRefPubMedGoogle Scholar
  126. 126.
    Hacisuleyman E, Goff LA, Trapnell C, Williams A, Henao-Mejia J et al (2014) Topological organization of multichromosomal regions by the long intergenic noncoding RNA Firre. Nat Struct Mol Biol 21:198–206PubMedCentralCrossRefPubMedGoogle Scholar
  127. 127.
    Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641CrossRefPubMedGoogle Scholar
  128. 128.
    Nagano T, Mitchell JA, Sanz LA, Pauler FM, Ferguson-Smith AC et al (2008) The Air noncoding RNA epigenetically silences transcription by targeting G9a to chromatin. Science 322:1717–1720CrossRefPubMedGoogle Scholar
  129. 129.
    Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X et al (2007) Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129:1311–1323PubMedCentralCrossRefPubMedGoogle Scholar
  130. 130.
    Pandey RR, Mondal T, Mohammad F, Enroth S, Redrup L et al (2008) Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell 32:232–246CrossRefPubMedGoogle Scholar
  131. 131.
    Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT (2008) Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science 322:750–756PubMedCentralCrossRefPubMedGoogle Scholar
  132. 132.
    Mohammad F, Mondal T, Guseva N, Pandey GK, Kanduri C (2010) Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1. Development 137:2493–2499CrossRefPubMedGoogle Scholar
  133. 133.
    Wu Y, Zhang L, Wang Y, Li H, Ren X et al (2015) Long non-coding RNA HOTAIR promotes tumor cell invasion and metastasis by recruiting EZH2 and repressing E-cadherin in oral squamous cell carcinoma. Int J Oncol 46:2586–2594PubMedGoogle Scholar
  134. 134.
    Khalil AM, Guttman M, Huarte M, Garber M, Raj A et al (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A 106:11667–11672PubMedCentralCrossRefPubMedGoogle Scholar
  135. 135.
    Zhao J, Ohsumi TK, Kung JT, Ogawa Y, Grau DJ et al (2010) Genome-wide identification of polycomb-associated RNAs by RIP-seq. Mol Cell 40:939–953PubMedCentralCrossRefPubMedGoogle Scholar
  136. 136.
    Brannan CI, Dees EC, Ingram RS, Tilghman SM (1990) The product of the H19 gene may function as an RNA. Mol Cell Biol 10:28–36PubMedCentralCrossRefPubMedGoogle Scholar
  137. 137.
    Brown CJ, Ballabio A, Rupert JL, Lafreniere RG, Grompe M et al (1991) A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature 349:38–44CrossRefPubMedGoogle Scholar
  138. 138.
    Simon MD, Pinter SF, Fang R, Sarma K, Rutenberg-Schoenberg M et al (2013) High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation. Nature 504:465–469PubMedCentralCrossRefPubMedGoogle Scholar
  139. 139.
    Chu C, Qu K, Zhong FL, Artandi SE, Chang HY (2011) Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol Cell 44:667–678PubMedCentralCrossRefPubMedGoogle Scholar
  140. 140.
    Arab K, Park YJ, Lindroth AM, Schafer A, Oakes C et al (2014) Long noncoding RNA TARID directs demethylation and activation of the tumor suppressor TCF21 via GADD45A. Mol Cell 55(4):604–614CrossRefPubMedGoogle Scholar
  141. 141.
    Tripathi V, Ellis JD, Shen Z, Song DY, Pan Q et al (2010) The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell 39:925–938PubMedCentralCrossRefPubMedGoogle Scholar
  142. 142.
    Bernard D, Prasanth KV, Tripathi V, Colasse S, Nakamura T et al (2010) A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression. EMBO J 29:3082–3093PubMedCentralCrossRefPubMedGoogle Scholar
  143. 143.
    Gong C, Maquat LE (2011) lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements. Nature 470:284–288PubMedCentralCrossRefPubMedGoogle Scholar
  144. 144.
    Yoon JH, Abdelmohsen K, Srikantan S, Yang X, Martindale JL et al (2012) LincRNA-p21 suppresses target mRNA translation. Mol Cell 47:648–655PubMedCentralCrossRefPubMedGoogle Scholar
  145. 145.
    Carrieri C, Cimatti L, Biagioli M, Beugnet A, Zucchelli S et al (2012) Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature 491:454–457CrossRefPubMedGoogle Scholar
  146. 146.
    Zappulla DC, Cech TR (2006) RNA as a flexible scaffold for proteins: yeast telomerase and beyond. Cold Spring Harb Symp Quant Biol 71:217–224CrossRefPubMedGoogle Scholar
  147. 147.
    Koziol MJ, Rinn JL (2010) RNA traffic control of chromatin complexes. Curr Opin Genet Dev 20:142–148PubMedCentralCrossRefPubMedGoogle Scholar
  148. 148.
    Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK et al (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329:689–693PubMedCentralCrossRefPubMedGoogle Scholar
  149. 149.
    Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG et al (2008) Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of beta-secretase. Nat Med 14:723–730PubMedCentralCrossRefPubMedGoogle Scholar
  150. 150.
    Carrieri C, Forrest AR, Santoro C, Persichetti F, Carninci P et al (2015) Expression analysis of the long non-coding RNA antisense to Uchl1 (AS Uchl1) during dopaminergic cells’ differentiation in vitro and in neurochemical models of Parkinson’s disease. Front Cell Neurosci 9:114PubMedCentralCrossRefPubMedGoogle Scholar
  151. 151.
    Ishii N, Ozaki K, Sato H, Mizuno H, Saito S et al (2006) Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction. J Hum Genet 51:1087–1099CrossRefPubMedGoogle Scholar
  152. 152.
    Pasmant E, Laurendeau I, Heron D, Vidaud M, Vidaud D et al (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 67:3963–3969CrossRefPubMedGoogle Scholar
  153. 153.
    Daughters RS, Tuttle DL, Gao W, Ikeda Y, Moseley ML et al (2009) RNA gain-of-function in spinocerebellar ataxia type 8. PLoS Genet 5:e1000600PubMedCentralCrossRefPubMedGoogle Scholar
  154. 154.
    Khalil AM, Faghihi MA, Modarresi F, Brothers SP, Wahlestedt C (2008) A novel RNA transcript with antiapoptotic function is silenced in fragile X syndrome. PLoS One 3:e1486PubMedCentralCrossRefPubMedGoogle Scholar
  155. 155.
    Prensner JR, Chinnaiyan AM (2011) The emergence of lncRNAs in cancer biology. Cancer Discov 1:391–407PubMedCentralCrossRefPubMedGoogle Scholar
  156. 156.
    Naemura M, Murasaki C, Inoue Y, Okamoto H, Kotake Y (2015) Long noncoding RNA ANRIL regulates proliferation of non-small cell lung cancer and cervical cancer cells. Anticancer Res 35:5377–5382PubMedGoogle Scholar
  157. 157.
    Cai Y, He J, Zhang D (2015) Long noncoding RNA CCAT2 promotes breast tumor growth by regulating the Wnt signaling pathway. Onco Targets Ther 8:2657–2664PubMedCentralPubMedGoogle Scholar
  158. 158.
    Zhuang Y, Nguyen HT, Burow ME, Zhuo Y, El-Dahr SS et al (2014) Elevated expression of long intergenic non-coding RNA HOTAIR in a basal-like variant of MCF-7 breast cancer cells. Mol Carcinog. 54(12):1656–1667PubMedCentralCrossRefPubMedGoogle Scholar
  159. 159.
    Gupta RA, Shah N, Wang KC, Kim J, Horlings HM et al (2010) Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 464:1071–1076PubMedCentralCrossRefPubMedGoogle Scholar
  160. 160.
    Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S et al (2011) Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res 71:6320–6326CrossRefPubMedGoogle Scholar
  161. 161.
    Chung S, Nakagawa H, Uemura M, Piao L, Ashikawa K et al (2011) Association of a novel long non-coding RNA in 8q24 with prostate cancer susceptibility. Cancer Sci 102:245–252CrossRefPubMedGoogle Scholar
  162. 162.
    Calin GA, Pekarsky Y, Croce CM (2007) The role of microRNA and other non-coding RNA in the pathogenesis of chronic lymphocytic leukemia. Best Pract Res Clin Haematol 20:425–437CrossRefPubMedGoogle Scholar
  163. 163.
    Calin GA, Liu CG, Ferracin M, Hyslop T, Spizzo R et al (2007) Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas. Cancer Cell 12:215–229CrossRefPubMedGoogle Scholar
  164. 164.
    Khaitan D, Dinger ME, Mazar J, Crawford J, Smith MA et al (2011) The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion. Cancer Res 71:3852–3862CrossRefPubMedGoogle Scholar
  165. 165.
    Li L, Feng T, Lian Y, Zhang G, Garen A et al (2009) Role of human noncoding RNAs in the control of tumorigenesis. Proc Natl Acad Sci U S A 106:12956–12961PubMedCentralCrossRefPubMedGoogle Scholar
  166. 166.
    Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ et al (2010) A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142:409–419PubMedCentralCrossRefPubMedGoogle Scholar
  167. 167.
    Yu W, Gius D, Onyango P, Muldoon-Jacobs K, Karp J et al (2008) Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA. Nature 451:202–206PubMedCentralCrossRefPubMedGoogle Scholar
  168. 168.
    Gutschner T, Hammerle M, Eissmann M, Hsu J, Kim Y et al (2013) The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res 73:1180–1189CrossRefPubMedGoogle Scholar
  169. 169.
    Tano K, Mizuno R, Okada T, Rakwal R, Shibato J et al (2010) MALAT-1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility-related genes. FEBS Lett 584:4575–4580CrossRefPubMedGoogle Scholar
  170. 170.
    Lopez-Ayllon BD, Moncho-Amor V, Abarrategi A, Ibanez de Caceres I, Castro-Carpeno J et al (2014) Cancer stem cells and cisplatin-resistant cells isolated from non-small-lung cancer cell lines constitute related cell populations. Cancer Med 3:1099–1111PubMedCentralCrossRefPubMedGoogle Scholar
  171. 171.
    Weber DG, Johnen G, Casjens S, Bryk O, Pesch B et al (2013) Evaluation of long noncoding RNA MALAT1 as a candidate blood-based biomarker for the diagnosis of non-small cell lung cancer. BMC Res Notes 6:518PubMedCentralCrossRefPubMedGoogle Scholar
  172. 172.
    Yao Y, Fan Y, Wu J, Wan H, Wang J et al (2012) Potential application of non-small cell lung cancer-associated autoantibodies to early cancer diagnosis. Biochem Biophys Res Commun 423:613–619PubMedCentralCrossRefPubMedGoogle Scholar
  173. 173.
    Guffanti A, Iacono M, Pelucchi P, Kim N, Solda G et al (2009) A transcriptional sketch of a primary human breast cancer by 454 deep sequencing. BMC Genomics 10:163PubMedCentralCrossRefPubMedGoogle Scholar
  174. 174.
    Kan JY, Wu DC, Yu FJ, Wu CY, Ho YW et al (2015) Chemokine (C-C motif) ligand 5 is involved in tumor-associated dendritic cell-mediated colon cancer progression through non-coding RNA MALAT-1. J Cell Physiol 230:1883–1894CrossRefPubMedGoogle Scholar
  175. 175.
    Fan Y, Shen B, Tan M, Mu X, Qin Y et al (2014) TGF-beta-induced upregulation of malat1 promotes bladder cancer metastasis by associating with suz12. Clin Cancer Res 20:1531–1541CrossRefPubMedGoogle Scholar
  176. 176.
    Okugawa Y, Toiyama Y, Hur K, Toden S, Saigusa S et al (2014) Metastasis-associated long non-coding RNA drives gastric cancer development and promotes peritoneal metastasis. Carcinogenesis 35:2731–2739PubMedCentralCrossRefPubMedGoogle Scholar
  177. 177.
    Hu L, Wu Y, Tan D, Meng H, Wang K et al (2015) Up-regulation of long noncoding RNA MALAT1 contributes to proliferation and metastasis in esophageal squamous cell carcinoma. J Exp Clin Cancer Res 34:7PubMedCentralCrossRefPubMedGoogle Scholar
  178. 178.
    Kuo IY, Wu CC, Chang JM, Huang YL, Lin CH et al (2014) Low SOX17 expression is a prognostic factor and drives transcriptional dysregulation and esophageal cancer progression. Int J Cancer 135:563–573CrossRefPubMedGoogle Scholar
  179. 179.
    Wang X, Li M, Wang Z, Han S, Tang X et al (2015) Silencing of long noncoding RNA MALAT1 by miR-101 and miR-217 inhibits proliferation, migration, and invasion of esophageal squamous cell carcinoma cells. J Biol Chem 290:3925–3935CrossRefPubMedGoogle Scholar
  180. 180.
    Mohamadkhani A (2014) Long noncoding RNAs in interaction with RNA binding proteins in hepatocellular carcinoma. Hepat Mon 14:e18794PubMedCentralCrossRefPubMedGoogle Scholar
  181. 181.
    Liu SP, Yang JX, Cao DY, Shen K (2013) Identification of differentially expressed long non-coding RNAs in human ovarian cancer cells with different metastatic potentials. Cancer Biol Med 10:138–141PubMedCentralPubMedGoogle Scholar
  182. 182.
    Ren S, Liu Y, Xu W, Sun Y, Lu J et al (2013) Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer. J Urol 190:2278–2287CrossRefPubMedGoogle Scholar
  183. 183.
    Sowalsky AG, Xia Z, Wang L, Zhao H, Chen S et al (2015) Whole transcriptome sequencing reveals extensive unspliced mRNA in metastatic castration-resistant prostate cancer. Mol Cancer Res 13:98–106CrossRefPubMedGoogle Scholar
  184. 184.
    Wang F, Ren S, Chen R, Lu J, Shi X et al (2014) Development and prospective multicenter evaluation of the long noncoding RNA MALAT-1 as a diagnostic urinary biomarker for prostate cancer. Oncotarget 5:11091–11102PubMedCentralCrossRefPubMedGoogle Scholar
  185. 185.
    Ellis MJ, Ding L, Shen D, Luo J, Suman VJ et al (2012) Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature 486:353–360PubMedCentralPubMedGoogle Scholar
  186. 186.
    Ji Q, Zhang L, Liu X, Zhou L, Wang W et al (2014) Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/PTBP2 complex. Br J Cancer 111:736–748PubMedCentralCrossRefPubMedGoogle Scholar
  187. 187.
    Xu C, Yang M, Tian J, Wang X, Li Z (2011) MALAT-1: a long non-coding RNA and its important 3′ end functional motif in colorectal cancer metastasis. Int J Oncol 39:169–175PubMedGoogle Scholar
  188. 188.
    Lin R, Roychowdhury-Saha M, Black C, Watt AT, Marcusson EG et al (2011) Control of RNA processing by a large non-coding RNA over-expressed in carcinomas. FEBS Lett 585:671–676PubMedCentralCrossRefPubMedGoogle Scholar
  189. 189.
    Yang L, Lin C, Liu W, Zhang J, Ohgi KA et al (2011) ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell 147:773–788PubMedCentralCrossRefPubMedGoogle Scholar
  190. 190.
    Loewen G, Jayawickramarajah J, Zhuo Y, Shan B (2014) Functions of lncRNA HOTAIR in lung cancer. J Hematol Oncol 7:90PubMedCentralCrossRefPubMedGoogle Scholar
  191. 191.
    Loewen G, Zhuo Y, Zhuang Y, Jayawickramarajah J, Shan B (2014) lincRNA HOTAIR as a novel promoter of cancer progression. J Can Res Updates 3:7Google Scholar
  192. 192.
    Zhuang Y, Wang X, Nguyen HT, Zhuo Y, Cui X et al (2013) Induction of long intergenic non-coding RNA HOTAIR in lung cancer cells by type I collagen. J Hematol Oncol 6:35PubMedCentralCrossRefPubMedGoogle Scholar
  193. 193.
    Svoboda M, Slyskova J, Schneiderova M, Makovicky P, Bielik L et al (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 35:1510–1515CrossRefPubMedGoogle Scholar
  194. 194.
    Chiyomaru T, Yamamura S, Fukuhara S, Yoshino H, Kinoshita T et al (2013) Genistein inhibits prostate cancer cell growth by targeting miR-34a and oncogenic HOTAIR. PLoS One 8:e70372PubMedCentralCrossRefPubMedGoogle Scholar
  195. 195.
    Xue X, Yang YA, Zhang A, Fong KW, Kim J et al (2016) LncRNA HOTAIR enhances ER signaling and confers tamoxifen resistance in breast cancer. Oncogene 35(21):2746–2755CrossRefPubMedGoogle Scholar
  196. 196.
    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 28:195–208CrossRefPubMedGoogle Scholar
  197. 197.
    Dimitrova N, Zamudio JR, Jong RM, Soukup D, Resnick R et al (2014) LincRNA-p21 activates p21 in cis to promote Polycomb target gene expression and to enforce the G1/S checkpoint. Mol Cell 54:777–790PubMedCentralCrossRefPubMedGoogle Scholar
  198. 198.
    Cai B, Wu Z, Liao K, Zhang S (2014) Long noncoding RNA HOTAIR can serve as a common molecular marker for lymph node metastasis: a meta-analysis. Tumour Biol 35(9):8445–8450CrossRefPubMedGoogle Scholar
  199. 199.
    Zheng HT, Shi DB, Wang YW, Li XX, Xu Y et al (2014) High expression of lncRNA MALAT1 suggests a biomarker of poor prognosis in colorectal cancer. Int J Clin Exp Pathol 7:3174–3181PubMedCentralPubMedGoogle Scholar
  200. 200.
    de Kok JB, Verhaegh GW, Roelofs RW, Hessels D, Kiemeney LA et al (2002) DD3(PCA3), a very sensitive and specific marker to detect prostate tumors. Cancer Res 62:2695–2698PubMedGoogle Scholar
  201. 201.
    Bussemakers MJ, van Bokhoven A, Verhaegh GW, Smit FP, Karthaus HF et al (1999) DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res 59:5975–5979PubMedGoogle Scholar
  202. 202.
    Nilsson J, Skog J, Nordstrand A, Baranov V, Mincheva-Nilsson L et al (2009) Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer. Br J Cancer 100:1603–1607PubMedCentralCrossRefPubMedGoogle Scholar
  203. 203.
    Kogure T, Yan IK, Lin WL, Patel T (2013) Extracellular vesicle-mediated transfer of a novel long noncoding RNA TUC339: a mechanism of intercellular signaling in human hepatocellular cancer. Genes Cancer 4:261–272PubMedCentralCrossRefPubMedGoogle Scholar
  204. 204.
    Zhuang Y, Nguyen HT, Burow ME, Zhuo Y, El-Dahr SS et al (2015) Elevated expression of long intergenic non-coding RNA HOTAIR in a basal-like variant of MCF-7 breast cancer cells. Mol Carcinog 54:1656–1667CrossRefPubMedGoogle Scholar
  205. 205.
    Pedram Fatemi R, Salah-Uddin S, Modarresi F, Khoury N, Wahlestedt C et al (2015) Screening for small-molecule modulators of long noncoding RNA-protein interactions using AlphaScreen. J Biomol Screen 20:1132–1141PubMedCentralCrossRefPubMedGoogle Scholar
  206. 206.
    Ng SY, Lin L, Soh BS, Stanton LW (2013) Long noncoding RNAs in development and disease of the central nervous system. Trends Genet 29:461–468CrossRefPubMedGoogle Scholar
  207. 207.
    Ng SY, Johnson R, Stanton LW (2012) Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors. EMBO J 31:522–533CrossRefPubMedGoogle Scholar
  208. 208.
    Modarresi F, Faghihi MA, Patel NS, Sahagan BG, Wahlestedt C et al (2011) Knockdown of BACE1-AS Nonprotein-coding transcript modulates beta-amyloid-related hippocampal neurogenesis. Int J Alzheimers Dis 2011:929042PubMedCentralPubMedGoogle Scholar
  209. 209.
    Muddashetty R, Khanam T, Kondrashov A, Bundman M, Iacoangeli A et al (2002) Poly(A)-binding protein is associated with neuronal BC1 and BC200 ribonucleoprotein particles. J Mol Biol 321:433–445CrossRefPubMedGoogle Scholar
  210. 210.
    Mus E, Hof PR, Tiedge H (2007) Dendritic BC200 RNA in aging and in Alzheimer’s disease. Proc Natl Acad Sci U S A 104:10679–10684PubMedCentralCrossRefPubMedGoogle Scholar
  211. 211.
    Morais VA, Verstreken P, Roethig A, Smet J, Snellinx A et al (2009) Parkinson's disease mutations in PINK1 result in decreased Complex I activity and deficient synaptic function. EMBO Mol Med 1:99–111PubMedCentralCrossRefPubMedGoogle Scholar
  212. 212.
    Scheele C, Petrovic N, Faghihi MA, Lassmann T, Fredriksson K et al (2007) The human PINK1 locus is regulated in vivo by a non-coding natural antisense RNA during modulation of mitochondrial function. BMC Genomics 8:74PubMedCentralCrossRefPubMedGoogle Scholar
  213. 213.
    Herriges MJ, Swarr DT, Morley MP, Rathi KS, Peng T et al (2014) Long noncoding RNAs are spatially correlated with transcription factors and regulate lung development. Genes Dev 28:1363–1379PubMedCentralCrossRefPubMedGoogle Scholar
  214. 214.
    Szafranski P, Dharmadhikari AV, Brosens E, Gurha P, Kolodziejska KE et al (2013) Small noncoding differentially methylated copy-number variants, including lncRNA genes, cause a lethal lung developmental disorder. Genome Res 23:23–33PubMedCentralCrossRefPubMedGoogle Scholar
  215. 215.
    Michalik KM, You X, Manavski Y, Doddaballapur A, Zornig M et al (2014) Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res 114:1389–1397CrossRefPubMedGoogle Scholar
  216. 216.
    Yoon JH, Abdelmohsen K, Gorospe M (2014) Functional interactions among microRNAs and long noncoding RNAs. Semin Cell Dev Biol 34C:9–14CrossRefGoogle Scholar
  217. 217.
    de Giorgio A, Krell J, Harding V, Stebbing J, Castellano L (2013) Emerging roles of competing endogenous RNAs in cancer: insights from the regulation of PTEN. Mol Cell Biol 33:3976–3982PubMedCentralCrossRefPubMedGoogle Scholar
  218. 218.
    Wang Y, Xu Z, Jiang J, Xu C, Kang J et al (2013) Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Dev Cell 25:69–80CrossRefPubMedGoogle Scholar
  219. 219.
    Liu XH, Sun M, Nie FQ, Ge YB, Zhang EB et al (2014) Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer. Mol Cancer 13:92PubMedCentralCrossRefPubMedGoogle Scholar
  220. 220.
    Ma MZ, Li CX, Zhang Y, Weng MZ, Zhang MD et al (2014) Long non-coding RNA HOTAIR, a c-Myc activated driver of malignancy, negatively regulates miRNA-130a in gallbladder cancer. Mol Cancer 13:156PubMedCentralCrossRefPubMedGoogle Scholar
  221. 221.
    Zhou X, Ye F, Yin C, Zhuang Y, Yue G et al (2015) The interaction between MiR-141 and lncRNA-H19 in regulating cell proliferation and migration in gastric cancer. Cell Physiol Biochem 36:1440–1452CrossRefPubMedGoogle Scholar
  222. 222.
    Kallen AN, Zhou XB, Xu J, Qiao C, Ma J et al (2013) The imprinted H19 lncRNA antagonizes let-7 microRNAs. Mol Cell 52:101–112CrossRefPubMedGoogle Scholar
  223. 223.
    Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O et al (2011) A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147:358–369PubMedCentralCrossRefPubMedGoogle Scholar
  224. 224.
    Jeck WR, Sharpless NE (2014) Detecting and characterizing circular RNAs. Nat Biotechnol 32:453–461PubMedCentralCrossRefPubMedGoogle Scholar
  225. 225.
    Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B et al (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495:384–388CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  1. 1.Xuzhou College of MedicineXuzhouChina
  2. 2.Kadlec Regional Medical CenterRichlandUSA
  3. 3.Elson S. Floyd College of MedicineWashington State University SpokaneSpokaneUSA

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