Abstract
BackgroundChanges of miRNAs in exosome have been reported in different disease diagnosis and provided as potential biomarkers. In this study, we compared microRNA profile in exosomes in 5 MHFMD and 5 ESHFMD as well as in 5 healthy children.MethodsDifferent expression of miRNAs in exosomes across all the three groups were screened using miRNA microarray method. Further validated test was conducted through quantitative real-time PCR assays with 54 exosome samples (18 ESHFMD, 18 MHFMD, and 18 healthy control). The judgment accuracy was then estimated by the receiver operating characteristic (ROC) curve analysis; and the specificity and sensitivity were evaluated by the multiple logistic regression analysis.ResultsThere were 11 different miRNAs in exosomes of MHFMD and ESHFMD compared to healthy children, of which 4 were up-regulated and 7 were down-regulated. Further validation indicated that the 4 significant differentially expressed candidate miRNAs (miR-671-5p, miR-16-5p, miR-150-3p, and miR-4281) in exosome showed the same changes as in the microarray analysis, and the expression level of three miRNAs (miR-671-5p, miR-16-5p, and miR-150-3p) were significantly different between MHFMD or ESHFMD and the healthy controls. The accuracy of the test results were high with the under curve (AUC) value range from 0.79 to 1.00. They also provided a specificity of 72%-100% and a sensitivity of 78%-100%, which possessed ability to discriminate ESHFMD from MHFMD with the AUC value of 0.76-0.82.ConclusionsThis study indicated that the exosomal miRNA from patients with different condition of HFMD express unique miRNA profiles. Exosomal miRNA expression profiles may provide supplemental biomarkers for diagnosing and subtyping HFMD infections.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-506) contains supplementary material, which is available to authorized users.
Highlights
Changes of miRNAs in exosome have been reported in different disease diagnosis and provided as potential biomarkers
Exosome isolation and validation Microvesicles isolated from sera of controls and mild HFMD (MHFMD) and extremely severe HFMD (ESHFMD) patients were assessed by Transmission electron microscopy (TEM) and western blotting
The microarray results identified various miRNAs that were differentially regulated in the exosome of MHFMD and ESHFMD samples relative to healthy controls, and a scatter plot was generated (Figure 2A)
Summary
Changes of miRNAs in exosome have been reported in different disease diagnosis and provided as potential biomarkers. Secreted vesicles play an important role in normal physiological processes, development, and conditions such as viral infection [13,14,15] and are a possible source or pool of novel biomarkers of many diseases [16,17,18]. MiRNAs can be transferred by an exosomal route and further exert gene silencing in recipient cells [19,20], where they play an essential regulatory role during development, with their levels changing in different cell types and at different developmental stages [21,22]. Changes in exosomal miRNAs have been reported in patients diagnosed with Alzheimer’s disease (AD), and miRNAs have been shown to provide diagnostic biomarkers [26]
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