title: Integrated Analysis of Dysregulated ncRNA and mRNA Expression Profiles in Humans Exposed to Carbon Nanotubes.
abstract: BACKGROUND
  As the application of carbon nanotubes (CNT) in consumer products continues to rise, studies have expanded to determine the associated risks of exposure on human and environmental health. In particular, several lines of evidence indicate that exposure to multi-walled carbon nanotubes (MWCNT) could pose a carcinogenic risk similar to asbestos fibers. However, to date the potential markers of MWCNT exposure are not yet explored in humans.
  
  
  METHODS
  In the present study, global mRNA and ncRNA expression profiles in the blood of exposed workers, having direct contact with MWCNT aerosol for at least 6 months (n = 8), were compared with expression profiles of non-exposed (n = 7) workers (e.g., professional and/or technical staff) from the same manufacturing facility.
  
  
  RESULTS
  Significant changes in the ncRNA and mRNA expression profiles were observed between exposed and non-exposed worker groups. An integrative analysis of ncRNA-mRNA correlations was performed to identify target genes, functional relationships, and regulatory networks in MWCNT-exposed workers. The coordinated changes in ncRNA and mRNA expression profiles revealed a set of miRNAs and their target genes with roles in cell cycle regulation/progression/control, apoptosis and proliferation. Further, the identified pathways and signaling networks also revealed MWCNT potential to trigger pulmonary and cardiovascular effects as well as carcinogenic outcomes in humans, similar to those previously described in rodents exposed to MWCNTs.
  
  
  CONCLUSIONS
  This study is the first to investigate aberrant changes in mRNA and ncRNA expression profiles in the blood of humans exposed to MWCNT. The significant changes in several miRNAs and mRNAs expression as well as their regulatory networks are important for getting molecular insights into the MWCNT-induced toxicity and pathogenesis in humans. Further large-scale prospective studies are necessary to validate the potential applicability of such changes in mRNAs and miRNAs as prognostic markers of MWCNT exposures in humans.
authors.affiliation: Exposure Assessment Branch/HELD/NIOSH/CDC, Morgantown, WV - 26505, United States of America.|Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV -26505, United States of America.
authors.forename: Anna A
authors.initials: AA
authors.lastname: Shvedova
authors.affiliation: Exposure Assessment Branch/HELD/NIOSH/CDC, Morgantown, WV - 26505, United States of America.
authors.forename: Naveena
authors.initials: N
authors.lastname: Yanamala
authors.affiliation: Exposure Assessment Branch/HELD/NIOSH/CDC, Morgantown, WV - 26505, United States of America.
authors.forename: Elena R
authors.initials: ER
authors.lastname: Kisin
authors.affiliation: Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV -26505, United States of America.|Department of Hygiene and Occupational Health, Kazan State Medical University, ul. Butlerova 49, Kazan, 420012 Russia.
authors.forename: Timur O
authors.initials: TO
authors.lastname: Khailullin
authors.affiliation: NIOSH/CDC, 4676 Columbia Parkway, Cincinnati, OH - 45226, United States of America.
authors.forename: M Eileen
authors.initials: ME
authors.lastname: Birch
authors.affiliation: Department of Hygiene and Occupational Health, Kazan State Medical University, ul. Butlerova 49, Kazan, 420012 Russia.
authors.forename: Liliya M
authors.initials: LM
authors.lastname: Fatkhutdinova
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D037742:Nanotubes, Carbon / Q000009:adverse effects*; D016273:Occupational Exposure / Q000009:adverse effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D022661:RNA, Untranslated / Q000187:drug effects / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects*; D055815:Young Adult
chemical_list: D037742:Nanotubes, Carbon; D012333:RNA, Messenger; D022661:RNA, Untranslated