title: Epigenetic changes induced by air toxics: formaldehyde exposure alters miRNA expression profiles in human lung cells.
abstract: BACKGROUND
  Exposure to formaldehyde, a known air toxic, is associated with cancer and lung disease. Despite the adverse health effects of formaldehyde, the mechanisms underlying formaldehyde-induced disease remain largely unknown. Research has uncovered microRNAs (miRNAs) as key posttranscriptional regulators of gene expression that may influence cellular disease state. Although studies have compared different miRNA expression patterns between diseased and healthy tissue, this is the first study to examine perturbations in global miRNA levels resulting from formaldehyde exposure.
  
  
  OBJECTIVE
  We investigated whether cellular miRNA expression profiles are modified by formaldehyde exposure to test the hypothesis that formaldehyde exposure disrupts miRNA expression levels within lung cells, representing a novel epigenetic mechanism through which formaldehyde may induce disease.
  
  
  METHODS
  Human lung epithelial cells were grown at air-liquid interface and exposed to gaseous formaldehyde at 1 ppm for 4 hr. Small RNAs and protein were collected and analyzed for miRNA expression using microarray analysis and for interleukin (IL-8) protein levels by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Gaseous formaldehyde exposure altered the miRNA expression profiles in human lung cells. Specifically, 89 miRNAs were significantly down-regulated in formaldehyde-exposed samples versus controls. Functional and molecular network analysis of the predicted miRNA transcript targets revealed that formaldehyde exposure potentially alters signaling pathways associated with cancer, inflammatory response, and endocrine system regulation. IL-8 release increased in cells exposed to formaldehyde, and results were confirmed by real-time polymerase chain reaction.
  
  
  CONCLUSIONS
  Formaldehyde alters miRNA patterns that regulate gene expression, potentially leading to the initiation of a variety of diseases.
authors.affiliation: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Rager
authors.forename: Lisa
authors.initials: L
authors.lastname: Smeester
authors.forename: Ilona
authors.initials: I
authors.lastname: Jaspers
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Sexton
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fry
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D002460:Cell Line; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005557:Formaldehyde / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D035683:MicroRNAs; D005557:Formaldehyde