Long non-coding RNAs (lncRNAs) and microRNAs are involved in numerous physio-pathological conditions included cancer. To better understand the molecular mechanism of the oral antitumor multikinase inhibitor sorafenib, we profiled the expression of a panel of lncRNAs and miRNAs by qPCR array in a sorafenib-treated hepatocellular carcinoma (HCC) cell line. Among the most affected ncRNAs, we found that sorafenib mediated the dysregulation of the lncRNAs GAS5, HOTTIP and HOXA-AS2 and the miR-126-3p, in a panel of human cancer cell lines (HCC, renal and breast carcinomas). By luciferase gene reporter assay, we discovered that GAS5 may act as a sponge for miR-126-3p in HCC cells. The expression level of GAS5 and miR-126-3p was verified in human liquid and/or solid biopsies from HCC patients. miR-126-3p expression in HCC tissues was decreased respect to their correspondent peritumoral tissues. The levels of plasmatic circulating miR-126-3p and GAS5 were significantly higher and lower in HCC patients compared to healthy subjects, respectively. This study highlighted the capability of sorafenib to modulate the expression of a wide range of ncRNAs and specifically, GAS5 and miR-126-3p were involved in the response to sorafenib of different cancer cell types.

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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