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

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Bioinformatics in MicroRNA Research

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1617))

Abstract

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.

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References

  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 22:1775–1789

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  PubMed  Google Scholar 

  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 75:843–854

    Article  CAS  PubMed  Google Scholar 

  4. Kozomara A, Griffiths-Jones S (2014) miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res 42:D68–D73

    Article  CAS  PubMed  Google Scholar 

  5. Lee Y, Kim M, Han J, Yeom KH, Lee S et al (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23:4051–4060

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 37:3464–3473

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Katahira J, Yoneda Y (2011) Nucleocytoplasmic transport of microRNAs and related small RNAs. Traffic 12:1468–1474

    Article  CAS  PubMed  Google Scholar 

  8. Bhayani MK, Calin GA, Lai SY (2012) Functional relevance of miRNA sequences in human disease. Mutat Res 731:14–19

    Article  CAS  PubMed  Google Scholar 

  9. Roberts TC (2014) The MicroRNA biology of the mammalian nucleus. Mol Ther Nucleic Acids 3:e188

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Hu G, Drescher KM, Chen XM (2012) Exosomal miRNAs: biological properties and therapeutic potential. Front Genet 3:56

    CAS  PubMed Central  PubMed  Google Scholar 

  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 9:654–659

    Article  CAS  PubMed  Google Scholar 

  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 380:161–171

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 20:278–288

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Zhou R, O'Hara SP, Chen XM (2011) MicroRNA regulation of innate immune responses in epithelial cells. Cell Mol Immunol 8:371–379

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 1820:940–948

    Article  CAS  PubMed  Google Scholar 

  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 2:282

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 155:1527–1539

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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:ra70

    Article  CAS  PubMed  Google Scholar 

  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 68:7846–7854

    Article  CAS  PubMed  Google Scholar 

  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 50:563–570

    Article  CAS  PubMed  Google Scholar 

  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 216:671–680

    Article  CAS  PubMed  Google Scholar 

  22. Friedman RC, Farh KK, Burge CB, Bartel DP (2009) Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19:92–105

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Agarwal V, Bell GW, Nam JW, Bartel DP (2015) Predicting effective microRNA target sites in mammalian mRNAs. eLife 4:e05005

    Article  PubMed Central  Google Scholar 

  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 13:1102–1107

    Article  CAS  PubMed  Google Scholar 

  25. Nottrott S, Simard MJ, Richter JD (2006) Human let-7a miRNA blocks protein production on actively translating polyribosomes. Nat Struct Mol Biol 13:1108–1114

    Article  CAS  PubMed  Google Scholar 

  26. Petersen CP, Bordeleau ME, Pelletier J, Sharp PA (2006) Short RNAs repress translation after initiation in mammalian cells. Mol Cell 21:533–542

    Article  CAS  PubMed  Google Scholar 

  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 309:1573–1576

    Article  CAS  PubMed  Google Scholar 

  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 102:16961–16966

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 11:1640–1647

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 20:1885–1898

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Wu L, Fan J, Belasco JG (2006) MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci U S A 103:4034–4039

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Guo H, Ingolia NT, Weissman JS, Bartel DP (2010) Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466:835–840

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 288:4334–4345

    Article  CAS  PubMed  Google Scholar 

  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 285:21496–21507

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 129:1141–1151

    Article  CAS  PubMed  Google Scholar 

  36. Stefani G, Slack FJ (2008) Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol 9:219–230

    Article  CAS  PubMed  Google Scholar 

  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 105:16230–16235

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 14:266–275

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 119:4034–4046

    Article  CAS  PubMed  Google Scholar 

  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:e39674

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 105:1608–1613

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 109:941–946

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Ha TY (2011) The role of MicroRNAs in regulatory T cells and in the immune response. Immune Netw 11:11–41

    Article  PubMed Central  PubMed  Google Scholar 

  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 99:15524–15529

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  PubMed  Google Scholar 

  46. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D et al (2005) A microRNA polycistron as a potential human oncogene. Nature 435:828–833

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 65:9628–9632

    Article  CAS  PubMed  Google Scholar 

  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 64:3753–3756

    Article  CAS  PubMed  Google Scholar 

  49. Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R et al (2005) RAS is regulated by the let-7 microRNA family. Cell 120:635–647

    Article  CAS  PubMed  Google Scholar 

  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 31:350–358

    Article  CAS  PubMed  Google Scholar 

  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 106:10746–10751

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 104:15472–15477

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 104:1604–1609

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 104:16170–16175

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 10:593–601

    Article  CAS  PubMed  Google Scholar 

  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 28:117–126

    CAS  PubMed Central  PubMed  Google Scholar 

  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 14:382–393

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 16:492–498

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 101:11755–11760

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Chan JA, Krichevsky AM, Kosik KS (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 65:6029–6033

    Article  CAS  PubMed  Google Scholar 

  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 70:4666–4675

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Ma L, Teruya-Feldstein J, Weinberg RA (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449:682–688

    Article  CAS  PubMed  Google Scholar 

  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 101:2999–3004

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 105:7269–7274

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Lee YS, Dutta A (2007) The tumor suppressor microRNA let-7 represses the HMGA2 oncogene. Genes Dev 21:1025–1030

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  66. Mayr C, Hemann MT, Bartel DP (2007) Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science 315:1576–1579

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 68:8535–8540

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 103:2257–2261

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  69. O'Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT (2005) c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435:839–843

    Article  CAS  PubMed  Google Scholar 

  70. Peter ME (2009) Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle 8:843–852

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 511:143–150

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 20:360–367

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  73. Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH et al (2010) The microRNA spectrum in 12 body fluids. Clin Chem 56:1733–1741

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  74. Taylor DD, Gercel-Taylor C (2008) MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol Oncol 110:13–21

    Article  CAS  PubMed  Google Scholar 

  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 10:1470–1476

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 58:1375–1381

    Article  CAS  PubMed  Google Scholar 

  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 127:118–126

    Article  CAS  PubMed  Google Scholar 

  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 25:1674–1680

    Article  CAS  PubMed  Google Scholar 

  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:e17745

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 105:849–859

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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:e92921

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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:R27

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 109:3024–3029

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 105:13021–13026

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 127:43–51

    Article  CAS  PubMed  Google Scholar 

  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 69:8332–8340

    Article  CAS  PubMed  Google Scholar 

  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:e31422

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  88. Ebert MS, Neilson JR, Sharp PA (2007) MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 4:721–726

    Article  CAS  PubMed  Google Scholar 

  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 12:247–256

    CAS  PubMed Central  PubMed  Google Scholar 

  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:e80707

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  91. Kuss AW, Chen W (2008) MicroRNAs in brain function and disease. Curr Neurol Neurosci Rep 8:190–197

    Article  CAS  PubMed  Google Scholar 

  92. Kim J, Inoue K, Ishii J, Vanti WB, Voronov SV et al (2007) A MicroRNA feedback circuit in midbrain dopamine neurons. Science 317:1220–1224

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  93. Gehrke S, Imai Y, Sokol N, Lu B (2010) Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Nature 466:637–641

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  94. Blennow K, de Leon MJ, Zetterberg H (2006) Alzheimer’s disease. Lancet 368:387–403

    Article  CAS  PubMed  Google Scholar 

  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 14:27–41

    Article  CAS  PubMed  Google Scholar 

  96. Maes OC, Chertkow HM, Wang E, Schipper HM (2009) MicroRNA: implications for Alzheimer disease and other human CNS disorders. Curr Genomics 10:154–168

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 28:1795–1809

    Article  CAS  PubMed  Google Scholar 

  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 4:481–512

    Article  CAS  PubMed  Google Scholar 

  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:e8898

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 105:6415–6420

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 33:422–428

    Article  CAS  PubMed  Google Scholar 

  102. Booton R, Lindsay MA (2014) Emerging role of MicroRNAs and long noncoding RNAs in respiratory disease. Chest 146:193–204

    Article  CAS  PubMed  Google Scholar 

  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 236:572–580

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 103:2208–2213

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 310:442–453

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 47:536–542

    Article  CAS  PubMed  Google Scholar 

  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 186:965–974

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 129:95–103

    Article  CAS  PubMed  Google Scholar 

  109. O'Connell RM, Rao DS, Baltimore D (2012) microRNA regulation of inflammatory responses. Annu Rev Immunol 30:295–312

    Article  CAS  PubMed  Google Scholar 

  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 182:220–229

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 187:397–405

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 207:1589–1597

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 45:287–294

    Article  CAS  PubMed  Google Scholar 

  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 180:484–493

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  115. Jiang X, Tsitsiou E, Herrick SE, Lindsay MA (2010) MicroRNAs and the regulation of fibrosis. FEBS J 277:2015–2021

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  116. Ezzie ME, Crawford M, Cho JH, Orellana R, Zhang S et al (2012) Gene expression networks in COPD: microRNA and mRNA regulation. Thorax 67:122–131

    Article  PubMed  Google Scholar 

  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 182:1020–1029

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 67:26–34

    Article  PubMed  Google Scholar 

  119. Cunningham F, Amode MR, Barrell D, Beal K, Billis K et al (2015) Ensembl 2015. Nucleic Acids Res 43:D662–D669

    Article  PubMed  Google Scholar 

  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 97:17–27

    Article  CAS  PubMed  Google Scholar 

  121. Rinn JL, Chang HY (2012) Genome regulation by long noncoding RNAs. Annu Rev Biochem 81:145–166

    Article  CAS  PubMed  Google Scholar 

  122. Shibayama Y, Fanucchi S, Magagula L, Mhlanga MM (2014) lncRNA and gene looping: what’s the connection? Transcription 5:e28658

    Article  PubMed Central  PubMed  Google Scholar 

  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 339:159–166

    Article  CAS  PubMed  Google Scholar 

  124. Zong X, Tripathi V, Prasanth KV (2011) RNA splicing control: yet another gene regulatory role for long nuclear noncoding RNAs. RNA Biol 8:968–977

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 493:231–235

    Article  CAS  PubMed  Google Scholar 

  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 21:198–206

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  127. Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641

    Article  CAS  PubMed  Google Scholar 

  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 322:1717–1720

    Article  CAS  PubMed  Google Scholar 

  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 129:1311–1323

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 32:232–246

    Article  CAS  PubMed  Google Scholar 

  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 322:750–756

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  132. Mohammad F, Mondal T, Guseva N, Pandey GK, Kanduri C (2010) Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1. Development 137:2493–2499

    Article  CAS  PubMed  Google Scholar 

  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 46:2586–2594

    CAS  PubMed  Google Scholar 

  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 106:11667–11672

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 40:939–953

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  136. Brannan CI, Dees EC, Ingram RS, Tilghman SM (1990) The product of the H19 gene may function as an RNA. Mol Cell Biol 10:28–36

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 349:38–44

    Article  CAS  PubMed  Google Scholar 

  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 504:465–469

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 44:667–678

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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):604–614

    Article  CAS  PubMed  Google Scholar 

  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 39:925–938

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 29:3082–3093

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  143. Gong C, Maquat LE (2011) lncRNAs transactivate STAU1-mediated mRNA decay by duplexing with 3′ UTRs via Alu elements. Nature 470:284–288

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  144. Yoon JH, Abdelmohsen K, Srikantan S, Yang X, Martindale JL et al (2012) LincRNA-p21 suppresses target mRNA translation. Mol Cell 47:648–655

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 491:454–457

    Article  CAS  PubMed  Google Scholar 

  146. Zappulla DC, Cech TR (2006) RNA as a flexible scaffold for proteins: yeast telomerase and beyond. Cold Spring Harb Symp Quant Biol 71:217–224

    Article  CAS  PubMed  Google Scholar 

  147. Koziol MJ, Rinn JL (2010) RNA traffic control of chromatin complexes. Curr Opin Genet Dev 20:142–148

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 329:689–693

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 14:723–730

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 9:114

    Article  PubMed Central  PubMed  Google Scholar 

  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 51:1087–1099

    Article  CAS  PubMed  Google Scholar 

  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 67:3963–3969

    Article  CAS  PubMed  Google Scholar 

  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:e1000600

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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:e1486

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  155. Prensner JR, Chinnaiyan AM (2011) The emergence of lncRNAs in cancer biology. Cancer Discov 1:391–407

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 35:5377–5382

    CAS  PubMed  Google Scholar 

  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 8:2657–2664

    PubMed Central  PubMed  Google Scholar 

  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):1656–1667

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 464:1071–1076

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 71:6320–6326

    Article  CAS  PubMed  Google Scholar 

  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 102:245–252

    Article  CAS  PubMed  Google Scholar 

  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 20:425–437

    Article  CAS  PubMed  Google Scholar 

  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 12:215–229

    Article  CAS  PubMed  Google Scholar 

  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 71:3852–3862

    Article  CAS  PubMed  Google Scholar 

  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 106:12956–12961

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 142:409–419

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 451:202–206

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 73:1180–1189

    Article  CAS  PubMed  Google Scholar 

  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 584:4575–4580

    Article  CAS  PubMed  Google Scholar 

  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 3:1099–1111

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 6:518

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 423:613–619

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 10:163

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 230:1883–1894

    Article  CAS  PubMed  Google Scholar 

  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 20:1531–1541

    Article  CAS  PubMed  Google Scholar 

  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 35:2731–2739

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 34:7

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 135:563–573

    Article  CAS  PubMed  Google Scholar 

  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 290:3925–3935

    Article  CAS  PubMed  Google Scholar 

  180. Mohamadkhani A (2014) Long noncoding RNAs in interaction with RNA binding proteins in hepatocellular carcinoma. Hepat Mon 14:e18794

    Article  PubMed Central  PubMed  Google Scholar 

  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 10:138–141

    CAS  PubMed Central  PubMed  Google Scholar 

  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 190:2278–2287

    Article  CAS  PubMed  Google Scholar 

  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 13:98–106

    Article  CAS  PubMed  Google Scholar 

  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 5:11091–11102

    Article  PubMed Central  PubMed  Google Scholar 

  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 486:353–360

    CAS  PubMed Central  PubMed  Google Scholar 

  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 111:736–748

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 39:169–175

    PubMed  Google Scholar 

  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 585:671–676

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 147:773–788

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  190. Loewen G, Jayawickramarajah J, Zhuo Y, Shan B (2014) Functions of lncRNA HOTAIR in lung cancer. J Hematol Oncol 7:90

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 3:7

    Google Scholar 

  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 6:35

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 35:1510–1515

    Article  CAS  PubMed  Google Scholar 

  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:e70372

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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):2746–2755

    Article  CAS  PubMed  Google Scholar 

  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 28:195–208

    Article  CAS  PubMed  Google Scholar 

  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 54:777–790

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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):8445–8450

    Article  CAS  PubMed  Google Scholar 

  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 7:3174–3181

    CAS  PubMed Central  PubMed  Google Scholar 

  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 62:2695–2698

    PubMed  Google Scholar 

  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 59:5975–5979

    CAS  PubMed  Google Scholar 

  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 100:1603–1607

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 4:261–272

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 54:1656–1667

    Article  CAS  PubMed  Google Scholar 

  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 20:1132–1141

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  206. Ng SY, Lin L, Soh BS, Stanton LW (2013) Long noncoding RNAs in development and disease of the central nervous system. Trends Genet 29:461–468

    Article  CAS  PubMed  Google Scholar 

  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 31:522–533

    Article  CAS  PubMed  Google Scholar 

  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 2011:929042

    PubMed Central  PubMed  Google Scholar 

  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 321:433–445

    Article  CAS  PubMed  Google Scholar 

  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 104:10679–10684

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 1:99–111

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 8:74

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 28:1363–1379

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 23:23–33

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 114:1389–1397

    Article  CAS  PubMed  Google Scholar 

  216. Yoon JH, Abdelmohsen K, Gorospe M (2014) Functional interactions among microRNAs and long noncoding RNAs. Semin Cell Dev Biol 34C:9–14

    Article  CAS  Google Scholar 

  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 33:3976–3982

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 25:69–80

    Article  CAS  PubMed  Google Scholar 

  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 13:92

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 13:156

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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 36:1440–1452

    Article  CAS  PubMed  Google Scholar 

  222. Kallen AN, Zhou XB, Xu J, Qiao C, Ma J et al (2013) The imprinted H19 lncRNA antagonizes let-7 microRNAs. Mol Cell 52:101–112

    Article  CAS  PubMed  Google Scholar 

  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 147:358–369

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  224. Jeck WR, Sharpless NE (2014) Detecting and characterizing circular RNAs. Nat Biotechnol 32:453–461

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  225. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B et al (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495:384–388

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Xuzhou College of Medicine, Xuzhou, Jiangsu, China

    Min Xue

  2. Kadlec Regional Medical Center, 888 Swift Boulevard, Richland, WA, USA

    Ying Zhuo

  3. Elson S. Floyd College of Medicine, Washington State University Spokane, 1495, Spokane, WA, 99210-1495, USA

    Bin Shan M.D., Ph.D.

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Correspondence to Bin Shan M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. School of Computing, University of South Alabama, Mobile, Alabama, USA

    Jingshan Huang

  2. Department of Pharmacology, University of South Alabama, Mobile, Alabama, USA

    Glen M. Borchert

  3. Department of Computer and Information Science, University of Oregon, Eugene, Oregon, USA

    Dejing Dou

  4. Department of Electrical Engineering and Computer Science, University of Kansas, Lawrence, Kansas, USA

    Jun (Luke) Huan

  5. School of Bioengineering, Qilu University of Technology, Jinan, Shandong, China

    Wenjun Lan

  6. Mitchel Cancer Institute, University of South Alabama, Mobile, Alabama, USA

    Ming Tan

  7. Department of Endocrinology, First Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, China

    Bin Wu

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Xue, M., Zhuo, Y., Shan, B. (2017). MicroRNAs, Long Noncoding RNAs, and Their Functions in Human Disease. In: Huang, J., et al. Bioinformatics in MicroRNA Research. Methods in Molecular Biology, vol 1617. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7046-9_1

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  • DOI: https://doi.org/10.1007/978-1-4939-7046-9_1

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7044-5

  • Online ISBN: 978-1-4939-7046-9

  • eBook Packages: Springer Protocols

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