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

Our plain-English summary of Integrated Analysis of Dysregulated ncRNA and mRNA Expression Profiles in Humans Exposed to Carbon Nanotubes, by A.A. Shvedova, N. Yanamala, E.R. Kisin, et al (PloS One, 2016).

The study

• Authors: A.A. Shvedova, N. Yanamala, E.R. Kisin, T.O. Khailullin, M.E. Birch, L.M. Fatkhutdinova
• Journal: PloS One
• Published: 2016;11(3):e0150628
• Cited by: 62 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

Conclusion: 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.

In plain English

This pilot study looked at workers at a factory making multi-walled carbon nanotubes (MWCNTs), Nanotech Center Ltd. in Tambov, Russia. It did not study asbestos. Drawing on earlier studies, the authors said their findings were compatible with an asbestos-like fibrogenic or carcinogenic potential of MWCNTs, and they used an asbestos microscopy method modified for nanotubes. Blood was tested from 8 MWCNT-exposed workers and 7 unexposed co-workers. The authors measured gene activity (mRNA) and regulatory RNAs (lncRNA and miRNA). Air sampling found nanotubes, with potential exposure above the NIOSH recommended limit of 1 μg/m3 elemental carbon (8-hour average). Compared with unexposed workers, the exposed group differed in 977 lncRNAs, 785 mRNAs and 11 miRNAs. The differences were larger in three more heavily exposed workers. Using databases, the authors linked these changes to effects reported in rodents, such as lung inflammation, fibrosis and cancer. A second laboratory method re-tested six genes: five changed in the same direction as before, and TGFβ1 changed the opposite way. The authors concluded that these RNA changes may be promising blood markers of MWCNT exposure but need further validation. They noted the small sample size.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Pilot cross-sectional comparison of blood RNA (gene expression) profiles between exposed and non-exposed workers at one facility, with workplace air sampling
• Who was studied: 8 workers exposed to MWCNTs and 7 non-exposed controls from the same facility
• Exposure: Airborne multi-walled carbon nanotubes (MWCNTs) at the Nanotech Center Ltd. manufacturing facility in Tambov, Russia. Exposure was measured by air sampling for elemental carbon and by electron microscopy.
• Main results:
  • Electron microscopy used an asbestos method (NMAM 7402) modified mainly by dropping the steps needed to positively identify asbestos.
  • Air samples from the harvesting and packaging areas had an average inhalable elemental carbon concentration of about 14.42 plus or minus 3.8 μg/m3.
  • The authors reported that the measurements indicated potential MWCNT exposure above the NIOSH recommended exposure limit of 1 μg/m3 of elemental carbon as an 8-hour time-weighted average.
  • All exposed workers compared with non-exposed workers: 977 lncRNAs differed, 529 higher and 448 lower.
  • All exposed workers compared with non-exposed workers: 785 mRNAs (genes) differed, 292 higher and 493 lower.
  • All exposed workers compared with non-exposed workers: 11 miRNAs differed, 7 higher and 4 lower.
  • The changes were more prominent in three workers (TB1, TB2, TB14) estimated to have higher exposure. In this high-exposure group, 2404 lncRNAs, 2655 mRNAs and 29 miRNAs differed from the non-exposed group.
  • Using database analysis, the authors linked 11 mRNAs and 3 miRNAs in the overall exposed group, and 62 mRNAs and 4 miRNAs in the high-exposure group, to lung inflammation and/or pulmonary fibrosis as described in rodents.
  • In the authors' interpretation, the functional analysis suggested MWCNT potential to trigger cancer and other lung disease outcomes in humans, similar to those seen in rodent models.
  • Citing earlier studies, the authors wrote that their findings were compatible with a fibrogenic and/or carcinogenic potential of MWCNTs in humans similar to that of asbestos fibers.
  • Network analysis identified the cell-cycle gene Cyclin D1 (CCND1) as a central (hub) gene.
  • Re-testing by qRT-PCR: five of six genes showed the same direction of change as the microarray, and four of these were statistically significant. Overall agreement was Pearson r = 0.79, P less than 0.05.
  • For TGFβ1, the qRT-PCR result went in the opposite direction from the microarray result.
• The authors' conclusion: The authors concluded that the miRNA changes, together with their mRNA targets, have promising potential as blood markers for monitoring MWCNT exposure, but that their prognostic value still needs further validation.
• Limitations the authors state:
  • The authors state that the study has several limitations, including small sample size.
  • The authors state that a larger prospective study is needed, with repeated blood sampling over longer periods at multiple manufacturing sites, to corroborate the findings.
  • The authors state that the role of confounding factors such as age, sex and smoking history still needs to be examined.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenic, Apoptosis.

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