Differentially Expressed miRNAs and Functional Pathways Changes in Human Alveolar Epithelial Cells After 1 and 7 Days Exposure to MWCNT-7 or Asbestos

Ventura, Célia; Vieira, Luís; Silva, Catarina; Silva, Maria João

http://hdl.handle.net/10400.18/7450

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Abstract(s)

Environmental and occupational exposure to multi-walled carbon nanotubes (MWCNT), an engineered nanomaterial widely used in industrial and biomedical applications, has been associated with pulmonary adverse effects upon inhalation. Particularly, MWCNT-7 (Mitsui-7) has been classified as possibly carcinogenic to humans, and many toxicological studies have compared it with asbestos due to their similarity in physical characteristics and biopersistence, and the well-known pulmonary adverse effects of asbestos. Several pulmonary diseases have been associated with miRNA expression changes, thus, in this study, we compare the differentially expressed miRNAs (DEmiRNAs) and enriched KEGG pathways after 1 and 7 days exposure to MWCNT-7 or crocidolite, in order to understand the mechanisms of biological response to these materials over time and their possible similarity. For this purpose, miRNAs were sequenced in exposed and non-exposed A549 cells at both time points by next-generation sequencing, and the enriched cellular pathways identified as previously described with minor modifications1. A higher number of DEmiRNAs was observed at 24 h compared to 7 days (17 vs. 3 and 21 vs. 10 for MWCNT-7 and crocidolite, respectively). Accordingly, the number of enriched pathways was also higher at 24 h (23 vs. 30 at 24 h and 7 vs. 5 at 7 days for MWCNT-7 and crocidolite, respectively). At 7 days, most altered pathways were related to cancer, highlighting the carcinogenic potential of MWCNT-7 and crocidolite. The reduction of the number of affected functional pathways likely reflects a greatest impact of these materials shortly after exposure and/or that the differences in DEmiRNAs between non-exposed and exposed cells are less significant after long-term culture. 1Ventura et al, Toxicology Letters 328: 7-18