title: Disruption of microRNA expression in human airway cells by diesel exhaust particles is linked to tumorigenesis-associated pathways.
abstract: BACKGROUND
  Particulate matter (PM) is associated with adverse airway health effects; however, the underlying mechanism in disease initiation is still largely unknown. Recently, microRNAs (miRNAs; small noncoding RNAs) have been suggested to be important in maintaining the lung in a disease-free state through regulation of gene expression. Although many studies have shown aberrant miRNA expression patterns in diseased versus healthy tissue, little is known regarding whether environmental agents can induce such changes.
  
  
  OBJECTIVE
  We used diesel exhaust particles (DEP), the largest source of emitted airborne PM, to investigate pollutant-induced changes in miRNA expression in airway epithelial cells. We hypothesized that DEP exposure can lead to disruption of normal miRNA expression patterns, representing a plausible novel mechanism through which DEP can mediate disease initiation.
  
  
  METHODS
  Human bronchial epithelial cells were grown at air-liquid interface until they reached mucociliary differentiation. After treating the cells with 10 microg/cm(2) DEP for 24 hr, we analyzed total RNA for miRNA expression using microarray profile analysis and quantitative real-time polymerase chain reaction.
  
  
  RESULTS
  DEP exposure changed the miRNA expression profile in human airway epithelial cells. Specifically, 197 of 313 detectable miRNAs (62.9%) were either up-regulated or down-regulated by 1.5-fold. Molecular network analysis of putative targets of the 12 most altered miRNAs indicated that DEP exposure is associated with inflammatory responses pathways and a strong tumorigenic disease signature.
  
  
  CONCLUSIONS
  Alteration of miRNA expression profiles by environmental pollutants such as DEP can modify cellular processes by regulation of gene expression, which may lead to disease pathogenesis.
authors.affiliation: Human Studies Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Chapel Hill, North Carolina 27514, USA. jardim.melanie@epa.gov
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Jardim
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fry
authors.forename: Ilona
authors.initials: I
authors.lastname: Jaspers
authors.forename: Lisa
authors.initials: L
authors.lastname: Dailey
authors.forename: David
authors.initials: D
authors.lastname: Diaz-Sanchez
mesh_terms: D000328:Adult; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced; D035683:MicroRNAs / Q000187:drug effects* / Q000378:metabolism; D046228:Microarray Analysis / Q000379:methods; D052638:Particulate Matter / Q000633:toxicity; D016133:Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D035683:MicroRNAs; D052638:Particulate Matter; D001335:Vehicle Emissions