Open Access

Analysis of a nanoparticle‑enriched fraction of plasma reveals miRNA candidates for Down syndrome pathogenesis

  • Authors:
    • Alessandro Salvi
    • Marika Vezzoli
    • Sara Busatto
    • Lucia Paolini
    • Teresa Faranda
    • Edoardo Abeni
    • Maria Caracausi
    • Francesca Antonaros
    • Allison Piovesan
    • Chiara Locatelli
    • Guido Cocchi
    • Gualtiero Alvisi
    • Giuseppina De Petro
    • Doris Ricotta
    • Paolo Bergese
    • Annalisa Radeghieri
  • View Affiliations

  • Published online on: April 9, 2019     https://doi.org/10.3892/ijmm.2019.4158
  • Pages: 2303-2318
  • Copyright: © Salvi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Down syndrome (DS) is caused by the presence of part or all of a third copy of chromosome 21. DS is associated with several phenotypes, including intellectual disability, congenital heart disease, childhood leukemia and immune defects. Specific microRNAs (miRNAs/miR) have been described to be associated with DS, although none of them so far have been unequivocally linked to the pathology. The present study focuses to the best of our knowledge for the first time on the miRNAs contained in nanosized RNA carriers circulating in the blood. Fractions enriched in nanosized RNA‑carriers were separated from the plasma of young participants with DS and their non‑trisomic siblings and miRNAs were extracted. A microarray‑based analysis on a small cohort of samples led to the identification of the three most abundant miRNAs, namely miR‑16‑5p, miR‑99b‑5p and miR‑144‑3p. These miRNAs were then profiled for 15 pairs of DS and non‑trisomic sibling couples by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Results identified a clear differential expression trend of these miRNAs in DS with respect to their non‑trisomic siblings and gene ontology analysis pointed to their potential role in a number of typical DS features, including ‘nervous system development’, ‘neuronal cell body’ and certain forms of ‘leukemia’. Finally, these expression levels were associated with certain typical quantitative and qualitative clinical features of DS. These results contribute to the efforts in defining the DS‑associated pathogenic mechanisms and emphasize the importance of properly stratifying the miRNA fluid vehicles in order to probe biomolecules that are otherwise hidden and/or not accessible to (standard) analysis.

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APA
Salvi, A., Vezzoli, M., Busatto, S., Paolini, L., Faranda, T., Abeni, E. ... Radeghieri, A. (2019). Analysis of a nanoparticle‑enriched fraction of plasma reveals miRNA candidates for Down syndrome pathogenesis. International Journal of Molecular Medicine, 43, 2303-2318. https://doi.org/10.3892/ijmm.2019.4158
MLA
Salvi, A., Vezzoli, M., Busatto, S., Paolini, L., Faranda, T., Abeni, E., Caracausi, M., Antonaros, F., Piovesan, A., Locatelli, C., Cocchi, G., Alvisi, G., De Petro, G., Ricotta, D., Bergese, P., Radeghieri, A."Analysis of a nanoparticle‑enriched fraction of plasma reveals miRNA candidates for Down syndrome pathogenesis". International Journal of Molecular Medicine 43.6 (2019): 2303-2318.
Chicago
Salvi, A., Vezzoli, M., Busatto, S., Paolini, L., Faranda, T., Abeni, E., Caracausi, M., Antonaros, F., Piovesan, A., Locatelli, C., Cocchi, G., Alvisi, G., De Petro, G., Ricotta, D., Bergese, P., Radeghieri, A."Analysis of a nanoparticle‑enriched fraction of plasma reveals miRNA candidates for Down syndrome pathogenesis". International Journal of Molecular Medicine 43, no. 6 (2019): 2303-2318. https://doi.org/10.3892/ijmm.2019.4158