Differential modulation of vesicular and non-vesicular associated microRNAs isolated from sera of partially hepatectomized rats

Cell-free circulating microRNAs are protected from degradation by their association with either component of the RNAi machinery or vesicles. Although increasing evidences shows that different types of vesicles are capable of transporting microRNAs, current research mainly focuses on the characterization of exosomal microRNAs. Reason for this is that exosomal-microRNAs are thought to directly participate in intercellular communication. However, is yet unclear whether exosomal-microRNAs are also the most reliable source for discovering disease-associated biomarker. In this study, the distribution of circulating microRNAs associated to either the vesicular or non-vesicular fractions of sera isolated from partially hepatectomized rats was measured. Here we show that independently from their origin, levels of cell-free miR-122, miR-192, miR-194 and Let-7a are upregulated two days after partial hepatectomy. The inflammation-associated miR-150 and miR-155 are upregulated in the vesicular-fraction only, while the regeneration-associated miR-21 and miR-33 are upregulated in the vesicular- and downregulated in the non-vesicular fraction. Our study shows for the first time the modulation of microRNAs contained in the non-vesicular fraction. Overall, these findings suggest that, in the search for novel disease-associated biomarkers, the investigation of either vesicular or non-vesicular microRNAs may be more informative compared to the analysis of microRNAs isolated from unfractionated serum.

Corresponding author: Castoldi, Mirco

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