Integrated Analysis of Dysregulated ncRNA and mRNA Expression Profiles in Humans Exposed to Carbon Nanotubes

Abstract

BackgroundAs 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.MethodsIn 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.ResultsSignificant 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.ConclusionThis 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.

Fibrosis biomarkers in workers exposed to MWCNTs

“…The EC content (quartz filters) was determined by thermaloptical analysis, using a modified method NIOSH 5040 (Birch et al, 2011; NIOSH, 2013). The 8-hour time-weighted average (8-h TWA) EC concentrations were calculated for each worker taking into account the person's duties and time spent at different workstations, as described in detail in Shvedova et al (2016).…”

“…In these studies, the results of exposure to NM other than MWCNTs were analyzed; one common limitation of these studies was inconsistent assessments or low/short-interval exposures which has been discussed in detail in a recent review (Liou et al, 2015). Our recent pilot cross-sectional study (Shvedova et al, 2016) revealed changes in mRNA expression profiles of whole blood samples derived from workers exposed to MWCNT aerosol. Expression analysis revealed augmented levels of several fibrotic bio-markers including TGF-β, KL-6 in whole blood samples of workers exposed to MWCNTs.…”

Cardiovascular effects among workers exposed to multiwalled carbon nanotubes

“…However, interpretation of the results is hindered due to the limited characterisation of the MWCNT exposure in many of these studies and due to the small number of exposed individuals included (generally <10). Reported biological effects of MWCNT in exposed humans include oxidative stress markers,9 lung inflammation markers7 8 11 (including monocyte cell counts) and gene expression changes including messenger-RNA and non-coding RNA 10. No associations between MWCNT exposure and lung function,9 11 monocyte cell counts9 and pneumoproteins11 were found, which partly contradicts with the reported biological effects.…”

Human Asthmatic Bronchial Cells Are More Susceptible to Subchronic Repeated Exposures of Aerosolized Carbon Nanotubes At Occupationally Relevant Doses Than Healthy Cells

“…Results revealed significant changes in gene expression associated with cell-cycle regulation, apoptosis, and proliferation, with potential pulmonary, cardiovascular, and carcinogenic risk in MWCNT-exposed humans. 5 The extremely high aspect ratio and biopersistence of MWCNTs pose a major concern that fiber inhalation in the workplace might induce unwanted pulmonary effects that resemble the serious effects of micrometer-sized asbestos fibers. 6 A growing number of animal studies have demonstrated that MWCNT inhalation is a highly potent trigger for the onset of airway injury, inflammation, fibrosis, and granuloma formation.…”