Analysis of a nanoparticleenriched fraction of plasma reveals miRNA candidates for Down syndrome pathogenesis.
Int J Mol Med
; 43(6): 2303-2318, 2019 Jun.
Article
en En
| MEDLINE
| ID: mdl-31017260
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 RNAcarriers were separated from the plasma of young participants with DS and their nontrisomic siblings and miRNAs were extracted. A microarraybased analysis on a small cohort of samples led to the identification of the three most abundant miRNAs, namely miR165p, miR99b5p and miR1443p. These miRNAs were then profiled for 15 pairs of DS and nontrisomic sibling couples by reverse transcriptionquantitative polymerase chain reaction (RTqPCR). Results identified a clear differential expression trend of these miRNAs in DS with respect to their nontrisomic 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 DSassociated 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Síndrome de Down
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Perfilación de la Expresión Génica
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MicroARNs
Tipo de estudio:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Qualitative_research
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Int J Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Italia