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.

Differential expression profiling of long non-coding RNA GAS5 and miR-126-3p in human cancer cells in response to sorafenib

“…Circulating ncRNAs have been described in different human body fluids, including serum/plasma and urine and are promising biomarkers for cancer risk assessment, diagnosis, prognosis, and to monitor the treatment response 47–50 . In this context, our results on circulating GAS5 and miR-126-3p would indicate their potential to be used to discriminate HCC patients from healthy subjects.…”

Fourier‐transform Infrared (FT‐IR) spectroscopy fingerprints subpopulations of extracellular vesicles of different sizes and cellular origin

“…According to the most recent papers and guidelines [2][3][4], these traditional definitions are too rigid, and do not take into account the overlapping size range, similar morphology and variable composition of EV subpopulations. Hence, current attempts to devise a more precise nomenclature for EVs are now emerging in literature, together with a huge effort to classify EVs in different subpopulations according to multiple parameters, such as size, density, protein composition, lipid content, RNA and DNA cargo, morphology, description of conditions and cell origin [3][4][5]. EV classification parameters are based on a set of molecular components and physical properties intended to be univocally characteristics of the target subpopulation.…”

Genome-wide miRNA profiling in plasma of pregnant women with down syndrome fetuses

“…As Down syndrome pregnancies are also complicated by abnormal placentation [57], exosomes released from such an impaired placenta could be also promising markers for early detection of Down syndrome fetuses from the maternal circulation. So far, miRNAs from circulating nanoparticles have only been studied in young individuals with DS and their siblings with promising results achieved [58].…”