Exploring the potential of microRNAs as biomarkers of effect of nanofibres using MWCNT-7-exposed alveolar cells

Ventura, Célia; Vieira, Luís; Silva, Catarina; Sousa-Uva, Antonio; Silva, Maria João

http://hdl.handle.net/10400.18/6769

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Background: In the last years, several diseases have been associated with alterations in microRNA (miRNA) expression, and miRNA profiling has proved to be useful to detect or evaluate disease progression. Moreover, there has been attempts to identify differentially expressed (DE) miRNA after exposure to toxicants that could be used as biomarkers of effect. Since human exposure to nanofibres, such as the MWCNT-7, has considerably increased due to their incorporation in several consumer products, this work explores the use of DE miRNA for monitoring human exposure to MWCNT-7 and their effects. Methods: We analyzed DE miRNAs in A549 alveolar cells following 24 hours exposure to an occupationally relevant dose of MWCNT-7. Total RNA was used to generate cDNA libraries for sequencing in MiSeq (Illumina). Differential expression analysis of miRNAs between non-exposed and exposed cells was performed using DESeq2 and EdgeR Exact Test. Results: Several under- and over-expressed miRNAs were sequenced in A549 cells after 24 h exposure to MWCNT-7. After filtering them according to the criteria adopted, a set of 17 DE miRNAs was identified. Some of these miRNAs have been reported as regulators of pathways related to cell growth, proliferation, differentiation and survival. Conclusions: Although more studies are needed, it is likely that the miRNA profile here identified may provide a novel biomarker of human exposure to MWCNT-7 by inhalation.