Current Environmental Health Reports

, Volume 3, Issue 3, pp 178–187 | Cite as

Environmental Health and Long Non-coding RNAs

Environmental Epigenetics (A Baccarelli, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Environmental Epigenetics


An individual’s risk of developing a common disease typically depends on an interaction of genetic and environmental factors. Epigenetic research is uncovering novel ways through which environmental factors such as diet, air pollution, and chemical exposure can affect our genes. DNA methylation and histone modifications are the most commonly studied epigenetic mechanisms. The role of long non-coding RNAs (lncRNAs) in epigenetic processes has been more recently highlighted. LncRNAs are defined as transcribed RNA molecules greater than 200 nucleotides in length with little or no protein-coding capability. While few functional lncRNAs have been well characterized to date, they have been demonstrated to control gene regulation at every level, including transcriptional gene silencing via regulation of the chromatin structure and DNA methylation. This review aims to provide a general overview of lncRNA function with a focus on their role as key regulators of health and disease and as biomarkers of environmental exposure.


LncRNA Disease Chemicals Toxicology Epigenetics Smoking 


Compliance with Ethical Standards

Conflict of Interest

Oskar Karlsson and Andrea A. Baccarelli declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Jorde, L, Genes, environment, lifestyle and common diseases. In pathophysiology: the biologic basis for disease in adults and children. In: McCance K, Huether S, editors. 2015, Elsevier Health Sciences. p. 164-182.Google Scholar
  2. 2.
    Wu S et al. Substantial contribution of extrinsic risk factors to cancer development. Nature. 2015.Google Scholar
  3. 3.
    Soto AM, Sonnenschein C. Environmental causes of cancer: endocrine disruptors as carcinogens. Nat Rev Endocrinol. 2010;6(7):363–70.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Das UN. Obesity: genes, brain, gut, and environment. Nutrition. 2010;26(5):459–73.PubMedCrossRefGoogle Scholar
  5. 5.
    Karlsson O, Lindquist NG. Melanin affinity and its possible role in neurodegeneration. J Neural Transm. 2013.Google Scholar
  6. 6.
    Vrijens K, Bollati V, Nawrot TS. MicroRNAs as potential signatures of environmental exposure or effect: a systematic review. Environ Health Perspect. 2015;123(5):399–411.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Baccarelli A, Bollati V. Epigenetics and environmental chemicals. Curr Opin Pediatr. 2009;21(2):243–51.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Lee HS. Impact of maternal diet on the epigenome during in utero life and the developmental programming of diseases in childhood and adulthood. Nutrients. 2015;7(11):9492–507.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Wang KC, Chang HY. Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011;43(6):904–14.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Bernstein E, Allis CD. RNA meets chromatin. Genes Dev. 2005;19(14):1635–55.PubMedCrossRefGoogle Scholar
  11. 11.
    Bracken AP, Helin K. Polycomb group proteins: navigators of lineage pathways led astray in cancer. Nat Rev Cancer. 2009;9(11):773–84.PubMedCrossRefGoogle Scholar
  12. 12.
    Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10(3):155–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Whitehead J, Pandey GK, Kanduri C. Regulation of the mammalian epigenome by long noncoding RNAs. Biochim Biophys Acta. 2009;1790(9):936–47.PubMedCrossRefGoogle Scholar
  14. 14.
    Sun BK, Deaton AM, Lee JT. A transient heterochromatic state in Xist preempts X inactivation choice without RNA stabilization. Mol Cell. 2006;21(5):617–28.PubMedCrossRefGoogle Scholar
  15. 15.
    Mohammad F et al. Kcnq1ot1 noncoding RNA mediates transcriptional gene silencing by interacting with Dnmt1. Development. 2010;137(15):2493–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol. 2011;21(6):354–61.PubMedCrossRefGoogle Scholar
  17. 17.
    Okazaki Y et al. Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature. 2002;420(6915):563–73.PubMedCrossRefGoogle Scholar
  18. 18.
    Djebali S et al. Landscape of transcription in human cells. Nature. 2012;489(7414):101–8.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Consortium EP et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007;447(7146):799–816.CrossRefGoogle Scholar
  20. 20.
    Kapranov P et al. RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science. 2007;316(5830):1484–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Consortium EP. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489(7414):57–74.CrossRefGoogle Scholar
  22. 22.
    Lipovich L, Johnson R, Lin CY. MacroRNA underdogs in a microRNA world: evolutionary, regulatory, and biomedical significance of mammalian long non-protein-coding RNA. Biochim Biophys Acta. 2010;1799(9):597–615.PubMedCrossRefGoogle Scholar
  23. 23.
    Khalil AM et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A. 2009;106(28):11667–72.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Brosius J. Waste not, want not--transcript excess in multicellular eukaryotes. Trends Genet. 2005;21(5):287–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Carninci P et al. The transcriptional landscape of the mammalian genome. Science. 2005;309(5740):1559–63.PubMedCrossRefGoogle Scholar
  26. 26.
    Brown CJ et al. A gene from the region of the human X inactivation centre is expressed exclusively from the inactive X chromosome. Nature. 1991;349(6304):38–44.PubMedCrossRefGoogle Scholar
  27. 27.
    Sleutels F, Zwart R, Barlow DP. The non-coding air RNA is required for silencing autosomal imprinted genes. Nature. 2002;415(6873):810–3.PubMedCrossRefGoogle Scholar
  28. 28.
    Rinn JL et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell. 2007;129(7):1311–23.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Gupta RA et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 2010;464(7291):1071–6.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Fatica A, Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet. 2014;15(1):7–21.PubMedCrossRefGoogle Scholar
  31. 31.
    Taft RJ, Pheasant M, Mattick JS. The relationship between non-protein-coding DNA and eukaryotic complexity. Bioessays. 2007;29(3):288–99.PubMedCrossRefGoogle Scholar
  32. 32.
    Ravasi T et al. Experimental validation of the regulated expression of large numbers of non-coding RNAs from the mouse genome. Genome Res. 2006;16(1):11–9.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Mercer TR et al. Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci U S A. 2008;105(2):716–21.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Cabili MN et al. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev. 2011;25(18):1915–27.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell. 2009;136(4):629–41.PubMedCrossRefGoogle Scholar
  36. 36.
    Heward JA, Lindsay MA. Long non-coding RNAs in the regulation of the immune response. Trends Immunol. 2014;35(9):408–19.PubMedCrossRefGoogle Scholar
  37. 37.
    Rinn JL, Chang HY. Genome regulation by long noncoding RNAs. Annu Rev Biochem. 2012;81:145–66.PubMedCrossRefGoogle Scholar
  38. 38.
    Batista PJ, Chang HY. Long noncoding RNAs: cellular address codes in development and disease. Cell. 2013;152(6):1298–307.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Guttman M, Rinn JL. Modular regulatory principles of large non-coding RNAs. Nature. 2012;482(7385):339–46.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Gutschner T, Diederichs S. The hallmarks of cancer: a long non-coding RNA point of view. RNA Biol. 2012;9(6):703–19.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Novikova IV, Hennelly SP, Sanbonmatsu KY. Sizing up long non-coding RNAs: do lncRNAs have secondary and tertiary structure? Bioarchitecture. 2012;2(6):189–99.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Beltran M et al. A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes Dev. 2008;22(6):756–69.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Tsai MC et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science. 2010;329(5992):689–93.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Clemson CM et al. An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol Cell. 2009;33(6):717–26.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Willingham AT et al. A strategy for probing the function of noncoding RNAs finds a repressor of NFAT. Science. 2005;309(5740):1570–3.PubMedCrossRefGoogle Scholar
  46. 46.
    Zhao J et al. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science. 2008;322(5902):750–6.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Carrieri C et al. Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat. Nature. 2012;491(7424):454–7.PubMedCrossRefGoogle Scholar
  48. 48.
    Wang J et al. CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer. Nucleic Acids Res. 2010;38(16):5366–83.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Cai X, Cullen BR. The imprinted H19 noncoding RNA is a primary microRNA precursor. RNA. 2007;13(3):313–6.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Czech B et al. An endogenous small interfering RNA pathway in Drosophila. Nature. 2008;453(7196):798–802.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Pang KC et al. Genome-wide identification of long noncoding RNAs in CD8+ T cells. J Immunol. 2009;182(12):7738–48.PubMedCrossRefGoogle Scholar
  52. 52.
    Smith CM, Steitz JA. Classification of gas5 as a multi-small-nucleolar-RNA (snoRNA) host gene and a member of the 5′-terminal oligopyrimidine gene family reveals common features of snoRNA host genes. Mol Cell Biol. 1998;18(12):6897–909.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Golden DE, Gerbasi VR, Sontheimer EJ. An inside job for siRNAs. Mol Cell. 2008;31(3):309–12.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Slavoff SA et al. Peptidomic discovery of short open reading frame-encoded peptides in human cells. Nat Chem Biol. 2013;9(1):59–64.PubMedCrossRefGoogle Scholar
  55. 55.
    Ingolia NT, Lareau LF, Weissman JS. Ribosome profiling of mouse embryonic stem cells reveals the complexity and dynamics of mammalian proteomes. Cell. 2011;147(4):789–802.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Maass PG, Luft FC, Bahring S. Long non-coding RNA in health and disease. J Mol Med. 2014;92(4):337–46.PubMedCrossRefGoogle Scholar
  57. 57.
    Geisler S, Coller J. RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts. Nat Rev Mol Cell Biol. 2013;14(11):699–712.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Briggs JA et al. Mechanisms of long non-coding RNAs in mammalian nervous system development, plasticity, disease, and evolution. Neuron. 2015;88(5):861–77.PubMedCrossRefGoogle Scholar
  59. 59.
    Marin-Bejar O et al. Pint lincRNA connects the p53 pathway with epigenetic silencing by the Polycomb repressive complex 2. Genome Biol. 2013;14(9):R104.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Panzitt K et al. Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA. Gastroenterology. 2007;132(1):330–42.PubMedCrossRefGoogle Scholar
  61. 61.
    Hatchell EC et al. SLIRP, a small SRA binding protein, is a nuclear receptor corepressor. Mol Cell. 2006;22(5):657–68.PubMedCrossRefGoogle Scholar
  62. 62.
    Lanz RB et al. Steroid receptor RNA activator stimulates proliferation as well as apoptosis in vivo. Mol Cell Biol. 2003;23(20):7163–76.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Wu Y et al. Long noncoding RNA HOTAIR involvement in cancer. Tumour Biol. 2014;35(10):9531–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Kogo R et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 2011;71(20):6320–6.PubMedCrossRefGoogle Scholar
  65. 65.
    Carter G et al. Circulating long noncoding RNA GAS5 levels are correlated to prevalence of type 2 diabetes mellitus. BBA Clin. 2015;4:102–7.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Kino T et al. Noncoding RNA gas5 is a growth arrest- and starvation-associated repressor of the glucocorticoid receptor. Sci Signal. 2010;3(107):ra8.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Mourtada-Maarabouni M et al. GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer. Oncogene. 2009;28(2):195–208.PubMedCrossRefGoogle Scholar
  68. 68.
    Broadbent HM et al. Susceptibility to coronary artery disease and diabetes is encoded by distinct, tightly linked SNPs in the ANRIL locus on chromosome 9p. Hum Mol Genet. 2008;17(6):806–14.PubMedCrossRefGoogle Scholar
  69. 69.
    Cunnington MS et al. Chromosome 9p21 SNPs associated with multiple disease phenotypes correlate with ANRIL expression. PLoS Genet. 2010;6(4):e1000899.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Holdt LM et al. ANRIL expression is associated with atherosclerosis risk at chromosome 9p21. Arterioscler Thromb Vasc Biol. 2010;30(3):620–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Zeggini E et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science. 2007;316(5829):1336–41.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Pasmant E et al. ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J. 2011;25(2):444–8.PubMedCrossRefGoogle Scholar
  73. 73.
    Congrains A et al. ANRIL: molecular mechanisms and implications in human health. Int J Mol Sci. 2013;14(1):1278–92.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Ishii N et al. Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction. J Hum Genet. 2006;51(12):1087–99.PubMedCrossRefGoogle Scholar
  75. 75.
    Yan B et al. lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA. Circ Res. 2015;116(7):1143–56.PubMedCrossRefGoogle Scholar
  76. 76.
    Liao J et al. LncRNA MIAT: myocardial infarction associated and more. Gene. 2016;578(2):158–61.PubMedCrossRefGoogle Scholar
  77. 77.
    Barry G et al. The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing. Mol Psychiatry. 2014;19(4):486–94.PubMedCrossRefGoogle Scholar
  78. 78.
    Faghihi MA et al. Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of beta-secretase. Nat Med. 2008;14(7):723–30.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Kerin T et al. A noncoding RNA antisense to moesin at 5p14.1 in autism. Sci Transl Med. 2012;4(128):128ra40.PubMedCrossRefGoogle Scholar
  80. 80.
    Wang K et al. Common genetic variants on 5p14.1 associate with autism spectrum disorders. Nature. 2009;459(7246):528–33.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Thai P et al. Characterization of a novel long noncoding RNA, SCAL1, induced by cigarette smoke and elevated in lung cancer cell lines. Am J Respir Cell Mol Biol. 2013;49(2):204–11.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Bhan A, Mandal SS. LncRNA HOTAIR: A master regulator of chromatin dynamics and cancer. Biochim Biophys Acta. 2015;1856(1):151–64.PubMedGoogle Scholar
  83. 83.
    Brunner AL et al. Transcriptional profiling of long non-coding RNAs and novel transcribed regions across a diverse panel of archived human cancers. Genome Biol. 2012;13(8):R75.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Archer K et al. Long non-coding RNAs as master regulators in cardiovascular diseases. Int J Mol Sci. 2015;16(10):23651–67.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    McPherson R et al. A common allele on chromosome 9 associated with coronary heart disease. Science. 2007;316(5830):1488–91.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Huang YS et al. Urinary Xist is a potential biomarker for membranous nephropathy. Biochem Biophys Res Commun. 2014;452(3):415–21.PubMedCrossRefGoogle Scholar
  87. 87.
    Carpenter S et al. A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013;341(6147):789–92.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Fitzgerald KA, Caffrey DR. Long noncoding RNAs in innate and adaptive immunity. Curr Opin Immunol. 2014;26:140–6.PubMedCrossRefGoogle Scholar
  89. 89.
    Huang X et al. Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genomics. 2013;14:319.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    van Balkom BW et al. Quantitative and qualitative analysis of small RNAs in human endothelial cells and exosomes provides insights into localized RNA processing, degradation and sorting. J Extracell Vesicles. 2015;4:26760.PubMedGoogle Scholar
  91. 91.
    Gezer U et al. Long non-coding RNAs with low expression levels in cells are enriched in secreted exosomes. Cell Biol Int. 2014;38(9):1076–9.PubMedGoogle Scholar
  92. 92.
    Song J et al. PBMC and exosome-derived HOTAIR is a critical regulator and potent marker for rheumatoid arthritis. Clin Exp Med. 2015;15(1):121–6.PubMedCrossRefGoogle Scholar
  93. 93.
    Sigdel KR et al. The emerging functions of long noncoding RNA in immune cells: autoimmune diseases. Int J Immunol Res. 2015;2015:848790.Google Scholar
  94. 94.
    Li Z et al. The long noncoding RNA THRIL regulates TNFalpha expression through its interaction with hnRNPL. Proc Natl Acad Sci U S A. 2014;111(3):1002–7.PubMedCrossRefGoogle Scholar
  95. 95.
    Tsitsiou E et al. Transcriptome analysis shows activation of circulating CD8+ T cells in patients with severe asthma. J Allergy Clin Immunol. 2012;129(1):95–103.PubMedCrossRefGoogle Scholar
  96. 96.
    Zhang H et al. Profiling of human CD4+ T-cell subsets identifies the TH2-specific noncoding RNA GATA3-AS1. J Allergy Clin Immunol. 2013;132(4):1005–8.PubMedCrossRefGoogle Scholar
  97. 97.
    Stuhlmuller B et al. Detection of oncofetal h19 RNA in rheumatoid arthritis synovial tissue. Am J Pathol. 2003;163(3):901–11.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Li B et al. Transcriptome analysis of psoriasis in a large case-control sample: RNA-seq provides insights into disease mechanisms. J Invest Dermatol. 2014;134(7):1828–38.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Liu Q et al. Long noncoding RNA related to cartilage injury promotes chondrocyte extracellular matrix degradation in osteoarthritis. Arthritis Rheum. 2014;66(4):969–78.CrossRefGoogle Scholar
  100. 100.
    Muller N et al. Interleukin-6 and tumour necrosis factor-alpha differentially regulate lincRNA transcripts in cells of the innate immune system in vivo in human subjects with rheumatoid arthritis. Cytokine. 2014;68(1):65–8.PubMedCrossRefGoogle Scholar
  101. 101.
    Messemaker TC et al. A novel long non-coding RNA in the rheumatoid arthritis risk locus TRAF1-C5 influences C5 mRNA levels. Genes Immun. 2015.Google Scholar
  102. 102.
    Sonkoly E et al. Identification and characterization of a novel, psoriasis susceptibility-related noncoding RNA gene, PRINS. J Biol Chem. 2005;280(25):24159–67.PubMedCrossRefGoogle Scholar
  103. 103.
    Szegedi K et al. Expression and functional studies on the noncoding RNA, PRINS. Int J Mol Sci. 2012;14(1):205–25.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Kornfeld JW, Bruning JC. Regulation of metabolism by long, non-coding RNAs. Front Genet. 2014;5:57.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Barthel A, Schmoll D. Novel concepts in insulin regulation of hepatic gluconeogenesis. Am J Physiol Endocrinol Metab. 2003;285(4):E685–92.PubMedCrossRefGoogle Scholar
  106. 106.
    Kameswaran V, Kaestner KH. The Missing lnc(RNA) between the pancreatic beta-cell and diabetes. Front Genet. 2014;5:200.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Thum T, Condorelli G. Long noncoding RNAs and microRNAs in cardiovascular pathophysiology. Circ Res. 2015;116(4):751–62.PubMedCrossRefGoogle Scholar
  108. 108.
    Wang P et al. Differential lncRNAmRNA coexpression network analysis revealing the potential regulatory roles of lncRNAs in myocardial infarction. Mol Med Rep. 2015.Google Scholar
  109. 109.
    Han P et al. A long noncoding RNA protects the heart from pathological hypertrophy. Nature. 2014;514(7520):102–6.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Klattenhoff CA et al. Braveheart, a long noncoding RNA required for cardiovascular lineage commitment. Cell. 2013;152(3):570–83.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Grote P et al. The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Dev Cell. 2013;24(2):206–14.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Wu C, Arora P. Long noncoding Mhrt RNA: molecular crowbar unravel insights into heart failure treatment. Circ Cardiovasc Genet. 2015;8(1):213–5.PubMedCrossRefGoogle Scholar
  113. 113.
    Derrien T et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 2012;22(9):1775–89.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Syrbe S et al. De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy. Nat Genet. 2015;47(4):393–9.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Talkowski ME et al. Disruption of a large intergenic noncoding RNA in subjects with neurodevelopmental disabilities. Am J Hum Genet. 2012;91(6):1128–34.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Zhao X et al. A long noncoding RNA contributes to neuropathic pain by silencing Kcna2 in primary afferent neurons. Nat Neurosci. 2013;16(8):1024–31.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Qiu C, Chen G, Cui Q. Towards the understanding of microRNA and environmental factor interactions and their relationships to human diseases. Sci Rep. 2012;2:318.PubMedPubMedCentralGoogle Scholar
  118. 118.
    Wang J, Cui Q. Specific roles of MicroRNAs in their interactions with environmental factors. J Nucleic Acids. 2012;2012:10.Google Scholar
  119. 119.
    Hou L, Wang D, Baccarelli A. Environmental chemicals and microRNAs. Mutat Res. 2011;714(1-2):105–12.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Santoro MG. Heat shock factors and the control of the stress response. Biochem Pharmacol. 2000;59(1):55–63.PubMedCrossRefGoogle Scholar
  121. 121.
    De Maio A. Heat shock proteins: facts, thoughts, and dreams. Shock. 1999;11(1):1–12.PubMedCrossRefGoogle Scholar
  122. 122.
    Wu C. Heat shock transcription factors: structure and regulation. Annu Rev Cell Dev Biol. 1995;11:441–69.PubMedCrossRefGoogle Scholar
  123. 123.
    Shamovsky I et al. RNA-mediated response to heat shock in mammalian cells. Nature. 2006;440(7083):556–60.PubMedCrossRefGoogle Scholar
  124. 124.
    Tani H, Torimura M. Development of cytotoxicity-sensitive human cells using overexpression of long non-coding RNAs. J Biosci Bioeng. 2015;119(5):604–8.PubMedCrossRefGoogle Scholar
  125. 125.
    Zhou Z et al. Long non-coding RNAs as novel expression signatures modulate DNA damage and repair in cadmium toxicology. Sci Rep. 2015;5:15293.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Jacob MD et al. Environmental cues induce a long noncoding RNA-dependent remodeling of the nucleolus. Mol Biol Cell. 2013;24(18):2943–53.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Tani H, Torimura M. Identification of short-lived long non-coding RNAs as surrogate indicators for chemical stress response. Biochem Biophys Res Commun. 2013;439(4):547–51.PubMedCrossRefGoogle Scholar
  128. 128.
    Tani H et al. Long non-coding RNAs as surrogate indicators for chemical stress responses in human-induced pluripotent stem cells. PLoS One. 2014;9(8):e106282.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Huarte M et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010;142(3):409–19.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Mizutani R et al. Identification and characterization of novel genotoxic stress-inducible nuclear long noncoding RNAs in mammalian cells. PLoS One. 2012;7(4):e34949.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.•
    Bhan A et al. Bisphenol-A and diethylstilbestrol exposure induces the expression of breast cancer associated long noncoding RNA HOTAIR in vitro and in vivo. J Steroid Biochem Mol Biol. 2014;141:160–70. This paper demonstrate that BPA and DES exposure alters the epigenetic programming of the HOTAIR promoter leading to its endocrine disruption in vitro and in vivo. PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    Liu Y et al. Epithelial-mesenchymal transition and cancer stem cells, mediated by a long non-coding RNA, HOTAIR, are involved in cell malignant transformation induced by cigarette smoke extract. Toxicol Appl Pharmacol. 2015;282(1):9–19.PubMedCrossRefGoogle Scholar
  133. 133.
    Tani H, Torimura M, Akimitsu N. The RNA degradation pathway regulates the function of GAS5 a non-coding RNA in mammalian cells. PLoS One. 2013;8(1):e55684.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.•
    Martinez-Guitarte JL, Planello R, Morcillo G. Overexpression of long non-coding RNAs following exposure to xenobiotics in the aquatic midge Chironomus riparius. Aquat Toxicol. 2012;110–111:84–90. This paper demonstrated for the first time the ability of BPA to increase lncRNA expression. PubMedCrossRefGoogle Scholar
  135. 135.•
    Bi H et al. Microarray analysis of long non-coding RNAs in COPD lung tissue. Inflamm Res. 2015;64(2):119–26. This paper indicates that smoking may alter the expression of lncRNAs in human lung tissue. PubMedCrossRefGoogle Scholar
  136. 136.
    Liu Y et al. Epigenetic silencing of p21 by long non-coding RNA HOTAIR is involved in the cell cycle disorder induced by cigarette smoke extract. Toxicol Lett. 2016;240(1):60–7.PubMedCrossRefGoogle Scholar
  137. 137.
    Lu L et al. Posttranscriptional silencing of the lncRNA MALAT1 by miR-217 inhibits the epithelial-mesenchymal transition via enhancer of zeste homolog 2 in the malignant transformation of HBE cells induced by cigarette smoke extract. Toxicol Appl Pharmacol. 2015;289(2):276–85.PubMedCrossRefGoogle Scholar
  138. 138.
    Franchini M, Mannucci PM. Air pollution and cardiovascular disease. Thromb Res. 2012;129(3):230–4.PubMedCrossRefGoogle Scholar
  139. 139.
    Kelly FJ, Fussell JC. Air pollution and airway disease. Clin Exp Allergy. 2011;41(8):1059–71.PubMedCrossRefGoogle Scholar
  140. 140.
    Takizawa H. Impact of air pollution on allergic diseases. Korean J Intern Med. 2011;26(3):262–73.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Breton C, Marutani A. Air pollution and epigenetics: recent findings. Curr Environ Health Rep. 2014;1(1):35–45.CrossRefGoogle Scholar
  142. 142.
    Stanek LW et al. Air pollution toxicology—a brief review of the role of the science in shaping the current understanding of air pollution health risks. Toxicol Sci. 2011;120 Suppl 1:S8–27.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  1. 1.Center for Molecular Medicine, Department of Clinical NeuroscienceKarolinska InstitutetStockholmSweden
  2. 2.Department of Environmental HealthHarvard T.H. Chan School of Public HealthBostonUSA

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