microRNAs: implications for air pollution research.

The purpose of this review is to provide an update of the current understanding on the role of microRNAs in mediating genetic responses to air pollutants and to contemplate on how these responses ultimately control susceptibility to ambient air pollution. Morbidity and mortality attributable to air pollution continues to be a growing public health concern worldwide. Despite several studies on the health effects of ambient air pollution, underlying molecular mechanisms of susceptibility and disease remain elusive. In the last several years, special attention has been given to the role of epigenetics in mediating, not only genetic and physiological responses to certain environmental insults, but also in regulating underlying susceptibility to environmental stressors. Epigenetic mechanisms control the expression of gene products, both basally and as a response to a perturbation, without affecting the sequence of DNA itself. These mechanisms include structural regulation of the chromatin structure, such as DNA methylation and histone modifications, and post-transcriptional gene regulation, such as microRNA mediated repression of gene expression. microRNAs are small noncoding RNAs that have been quickly established as key regulators of gene expression. As such, miRNAs have been found to control several cellular processes including apoptosis, proliferation and differentiation. More recently, research has emerged suggesting that changes in the expression of some miRNAs may be critical for mediating biological, and ultimately physiological, responses to air pollutants. Although the study of microRNAs, and epigenetics as a whole, has come quite far in the field of cancer, the understanding of how these mechanisms regulate gene-environment interactions to environmental exposures in everyday life is unclear. This article does not necessarily reflect the views and policies of the US EPA.

[1]  Gregory J. Hannon,et al.  MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies , 2005, Nature Cell Biology.

[2]  Michael K. Skinner,et al.  Epigenetic Transgenerational Actions of Endocrine Disruptors and Male Fertility , 2005, Science.

[3]  Wen-Hsiung Li,et al.  Human polymorphism at microRNAs and microRNA target sites , 2007, Proceedings of the National Academy of Sciences.

[4]  Pamela Ohman-Strickland,et al.  Respiratory effects of exposure to diesel traffic in persons with asthma. , 2007, The New England journal of medicine.

[5]  Ahmad M Khalil,et al.  RNA-protein interactions in human health and disease. , 2011, Seminars in cell & developmental biology.

[6]  P. Hopke,et al.  The complexities of air pollution regulation: the need for an integrated research and regulatory perspective. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[7]  B. Nemery,et al.  The Meuse Valley fog of 1930: an air pollution disaster , 2001, The Lancet.

[8]  Robin Holliday,et al.  Epigenetics: A Historical Overview , 2006, Epigenetics.

[9]  W. Mcdonnell,et al.  Proportion of moderately exercising individuals responding to low-level, multi-hour ozone exposure. , 1995, American journal of respiratory and critical care medicine.

[10]  S. Kleeberger,et al.  Linkage analysis of susceptibility to ozone-induced lung inflammation in inbred mice , 1997, Nature Genetics.

[11]  D. Bartel MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[12]  A. Kimball,et al.  Response to acute ozone exposure in healthy men. Results of a screening procedure. , 1995, American journal of respiratory and critical care medicine.

[13]  C. Harris,et al.  Genetic variation in microRNA networks: the implications for cancer research , 2010, Nature Reviews Cancer.

[14]  Akshay Sood,et al.  Wood smoke exposure and gene promoter methylation are associated with increased risk for COPD in smokers. , 2010, American journal of respiratory and critical care medicine.

[15]  Maode Lai,et al.  Non‐coding RNAs and their epigenetic regulatory mechanisms , 2010, Biology of the cell.

[16]  D L Davis,et al.  Reassessment of the lethal London fog of 1952: novel indicators of acute and chronic consequences of acute exposure to air pollution. , 2001, Environmental health perspectives.

[17]  Frank D. Gilliland,et al.  Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. , 2009, American journal of respiratory and critical care medicine.

[18]  Noah Nd,et al.  Letter: Meningococcal infections. , 1975 .

[19]  W. Mitzner,et al.  Genetic linkage analysis of susceptibility to particle exposure in mice. , 2000, American journal of respiratory cell and molecular biology.

[20]  Friedrich Miescher,et al.  Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells , 2009 .

[21]  George A Calin,et al.  Chemoprevention of Cigarette Smoke–Induced Alterations of MicroRNA Expression in Rat Lungs , 2010, Cancer Prevention Research.

[22]  U. Bhadra,et al.  MicroRNAs – micro in size but macro in function , 2008, The FEBS journal.

[23]  W. Filipowicz,et al.  Regulation of mRNA translation and stability by microRNAs. , 2010, Annual review of biochemistry.

[24]  Shweta Trivedi,et al.  Oxidants and the pathogenesis of lung diseases. , 2008, The Journal of allergy and clinical immunology.

[25]  X. Xi,et al.  Analysis of p16 Gene Mutation, Deletion and Methylation in Patients with Arseniasis Produced by Indoor Unventilated-Stove Coal Usage in Guizhou, China , 2007, Journal of toxicology and environmental health. Part A.

[26]  J. Schwartz,et al.  Exposure to Metal-Rich Particulate Matter Modifies the Expression of Candidate MicroRNAs in Peripheral Blood Leukocytes , 2010, Environmental health perspectives.

[27]  W P D LOGAN,et al.  Mortality in the London fog incident, 1952. , 1953, Lancet.

[28]  J. Ayres,et al.  Health effects of air pollution. , 2001, WHO chronicle.

[29]  George R. Douglas,et al.  Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location , 2008, Proceedings of the National Academy of Sciences.

[30]  A. Baccarelli,et al.  Global and gene‐specific promoter methylation changes are related to anti‐B[a]PDE‐DNA adduct levels and influence micronuclei levels in polycyclic aromatic hydrocarbon‐exposed individuals , 2009, International journal of cancer.

[31]  George A Calin,et al.  Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[32]  P Theerman,et al.  Donora, Pennsylvania: an environmental disaster of the 20th century. , 2001, American journal of public health.

[33]  Michael K. Skinner,et al.  Epigenetic Transgenerational Actions of Vinclozolin on Promoter Regions of the Sperm Epigenome , 2010, PloS one.

[34]  A. Nel,et al.  In vivo nasal challenge with diesel exhaust particles enhances expression of the CC chemokines rantes, MIP-1alpha, and MCP-3 in humans. , 2000, Clinical immunology.

[35]  S. Xi,et al.  Cigarette Smoke Induces C/EBP-β-Mediated Activation of miR-31 in Normal Human Respiratory Epithelia and Lung Cancer Cells , 2010, PloS one.

[36]  Francine Laden,et al.  Lung Cancer and Vehicle Exhaust in Trucking Industry Workers , 2008, Environmental health perspectives.

[37]  A. Saxon,et al.  Diesel exhaust particles induce local IgE production in vivo and alter the pattern of IgE messenger RNA isoforms. , 1994, The Journal of clinical investigation.

[38]  Clay B Marsh,et al.  MicroRNAs in the Pathogenesis of Lung Cancer , 2009, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[39]  W. Foster,et al.  Evidence for ozone-induced small-airway dysfunction: lack of menstrual-cycle and gender effects. , 1995, American journal of respiratory and critical care medicine.

[40]  Baohong Zhang,et al.  RDX Induces Aberrant Expression of MicroRNAs in Mouse Brain and Liver , 2008, Environmental health perspectives.

[41]  Antonella Zanobetti,et al.  Rapid DNA methylation changes after exposure to traffic particles. , 2009, American journal of respiratory and critical care medicine.

[42]  P. Bromberg,et al.  COX-2 expression induced by diesel particles involves chromatin modification and degradation of HDAC1. , 2007, American journal of respiratory cell and molecular biology.

[43]  S. Kleeberger,et al.  Genetic mechanisms of susceptibility to ozone‐induced lung disease , 2010, Annals of the New York Academy of Sciences.

[44]  Qinghua Sun,et al.  Contemporary Reviews in Cardiovascular Medicine Cardiovascular Effects of Ambient Particulate Air Pollution Exposure , 2010 .

[45]  D. Díaz-Sánchez,et al.  Biology of diesel exhaust effects on respiratory function. , 2005, The Journal of allergy and clinical immunology.

[46]  R. Fry,et al.  Disruption of MicroRNA Expression in Human Airway Cells by Diesel Exhaust Particles Is Linked to Tumorigenesis-Associated Pathways , 2009, Environmental health perspectives.

[47]  S. London,et al.  Gene by environment interaction and ambient air pollution. , 2010, Proceedings of the American Thoracic Society.

[48]  K. Berhane,et al.  Effects of in utero and environmental tobacco smoke exposure on lung function in boys and girls with and without asthma. , 2000, American journal of respiratory and critical care medicine.

[49]  Shuta Tomida,et al.  Reduced expression of Dicer associated with poor prognosis in lung cancer patients , 2005, Cancer science.

[50]  P. Boutros,et al.  microRNAs in adult rodent liver are refractory to dioxin treatment. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[51]  Joellen Lewtas,et al.  Air pollution combustion emissions: characterization of causative agents and mechanisms associated with cancer, reproductive, and cardiovascular effects. , 2007, Mutation research.

[52]  D. Díaz-Sánchez,et al.  The role of diesel exhaust particles and their associated polyaromatic hydrocarbons in the induction of allergic airway disease. , 1997, Allergy.

[53]  Anil Potti,et al.  An Integrated Approach to the Prediction of Chemotherapeutic Response in Patients with Breast Cancer , 2008, PloS one.

[54]  Thomas D. Schmittgen,et al.  Integrating the MicroRNome into the study of lung disease. , 2009, American journal of respiratory and critical care medicine.

[55]  B. Goldstein,et al.  Susceptibility of inbred mouse strains to ozone. , 1973, Archives of environmental health.

[56]  Jason H. Moore,et al.  Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. , 2007, Cancer research.

[57]  F. Perera,et al.  Combined inhaled diesel exhaust particles and allergen exposure alter methylation of T helper genes and IgE production in vivo. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[58]  A. Ledbetter,et al.  ST depression, arrhythmia, vagal dominance, and reduced cardiac micro-RNA in particulate-exposed rats. , 2011, American journal of respiratory cell and molecular biology.

[59]  R. Balasubramanian,et al.  Contrasting reactive oxygen species and transition metal concentrations in combustion aerosols. , 2007, Environmental research.

[60]  M. C. Liu,et al.  Ozone exposure in humans: inflammatory, small and peripheral airway responses. , 1995, American journal of respiratory and critical care medicine.

[61]  M. Green Air pollution and health , 1995 .

[62]  N. Iwai,et al.  Polymorphisms in human pre-miRNAs. , 2005, Biochemical and biophysical research communications.

[63]  Michael K Skinner,et al.  Transgenerational effect of the endocrine disruptor vinclozolin on male spermatogenesis. , 2006, Journal of andrology.

[64]  C. Koshland,et al.  Cellular response to diesel exhaust particles strongly depends on the exposure method. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[65]  Joel Schwartz,et al.  Prolonged Exposure to Particulate Pollution, Genes Associated with Glutathione Pathways, and DNA Methylation in a Cohort of Older Men , 2011, Environmental health perspectives.

[66]  J. Borlak,et al.  The next innovation cycle in toxicogenomics: environmental epigenetics. , 2008, Mutation research.

[67]  M. Fabbri,et al.  MicroRNAs and genomic variations: from Proteus tricks to Prometheus gift. , 2009, Carcinogenesis.

[68]  George A. Calin,et al.  Mammalian microRNAs: a small world for fine-tuning gene expression , 2006, Mammalian Genome.

[69]  S. De Flora,et al.  Dose-responsiveness and persistence of microRNA expression alterations induced by cigarette smoke in mouse lung. , 2011, Mutation research.

[70]  L. Hou,et al.  Changes in DNA methylation patterns in subjects exposed to low-dose benzene. , 2007, Cancer research.

[71]  R. Jirtle,et al.  Environmental epigenomics and disease susceptibility , 2007, Nature Reviews Genetics.

[72]  Andrew Williams,et al.  Lack of change in microRNA expression in adult mouse liver following treatment with benzo(a)pyrene despite robust mRNA transcriptional response. , 2011, Mutation research.

[73]  M. Skinner,et al.  Epigenetic transgenerational effects of endocrine disruptors on male reproduction. , 2009, Seminars in reproductive medicine.

[74]  Steffen Loft,et al.  Air pollution, oxidative damage to DNA, and carcinogenesis. , 2008, Cancer letters.

[75]  D. Diat-Sanchez,et al.  The role of diesel exhaust particles and their associated polyaromatic hydrocarbons in the induction of allergic airway disease , 1997 .

[76]  S. Ho,et al.  Environmental epigenetics and asthma: current concepts and call for studies. , 2008, American journal of respiratory and critical care medicine.

[77]  J. Schwartz,et al.  Effects of Particulate Matter on Genomic DNA Methylation Content and iNOS Promoter Methylation , 2008, Environmental health perspectives.

[78]  A. Saxon,et al.  Diesel exhaust particles directly induce activated mast cells to degranulate and increase histamine levels and symptom severity. , 2000, The Journal of allergy and clinical immunology.

[79]  Avrum Spira,et al.  MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium , 2009, Proceedings of the National Academy of Sciences.

[80]  S. Belinsky,et al.  Aberrant CpG island methylation of the p16(INK4a) and estrogen receptor genes in rat lung tumors induced by particulate carcinogens. , 2002, Carcinogenesis.

[81]  Andre Nel,et al.  Health effects of air pollution. , 2004, The Journal of allergy and clinical immunology.

[82]  W. Filipowicz,et al.  Relief of microRNA-Mediated Translational Repression in Human Cells Subjected to Stress , 2006, Cell.

[83]  Sun Mi Park,et al.  MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death , 2008, Oncogene.

[84]  M. Skinner,et al.  Endocrine disruptor vinclozolin induced epigenetic transgenerational adult-onset disease. , 2006, Endocrinology.

[85]  P. Vokonas,et al.  Black Carbon Exposures, Blood Pressure, and Interactions with Single Nucleotide Polymorphisms in MicroRNA Processing Genes , 2010, Environmental health perspectives.

[86]  M. Daly,et al.  Genetic analysis of ozone-induced acute lung injury in sensitive and resistant strains of mice , 1997, Nature Genetics.