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

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.

journal_name

Int J Mol Med

journal_title

International journal of molecular medicine

authors

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

doi

10.3892/ijmm.2019.4158

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

2303-2318

issue

eissn

1107-3756

issn

1791-244X

journal_volume

pub_type

杂志文章

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