Expression of microRNA-129-2-3p and microRNA-935 in plasma and brain tissue of human refractory epilepsy.

OBJECTIVE:Numerous microRNAs (miRNAs) are differentially expressed in specific diseases, suggesting possible use as diagnostic or prognostic biomarkers. The purpose of this study is to investigate the expression levels of miR-129-2-3p and miR-935 in cortical brain tissue and plasma samples from controls and refractory temporal lobe epilepsy (TLE) patients to evaluate the utility of these measures as diagnostic biomarkers. METHODS:The study was divided into three phases. First, cortical brain tissue samples from nine refractory TLE patients and eight controls were screened for differential miRNA expression using the Affymetrix miRNA 4.0 microarray. Second, real-time quantitative PCR (qRT-PCR) was used to verify the microarray results in brain tissue samples from 13 refractory TLE patients and 13 healthy controls (including those studied by microarray analysis). Third, we tested the expression levels of selected miRNAs in plasma samples from 25 refractory TLE patients and 25 healthy volunteers by qRT-PCR. The capacity of miR-129-2-3p and miR-935 expression to distinguish refractory TLE from health controls was tested by receiver operator characteristics (ROC) curve analysis. RESULTS:(1) High-resolution miRNA arrays indicated that miR-129-2-3p and miR-935 were significantly upregulated in the cortical brain tissues of TLE patients compared to controls. (2) qRT-PCR confirmed upregulated miR-129-2-3p expression in the brain tissue(P<0.0001) and plasma samples(P=0.0008) of refractory TLE patients. (3) The expression of miR-935 in epilepsy patients was higher than control group, however, there are no significant statistical differences between them whether in plasma samples(P=0.644) or in tissue samples(P=0.258). (4) ROC analysis of miRNA-129-2-3p showed that the area under the curve (AUC) was 0.929 (95% CI: 0.833-1.000; p=0.000) for brain tissue and 0.778 (95% CI: 0.640-0.915; p=0.001) for plasma. CONCLUSION:Expression of miRNA-129-2-3p was upregulated in cortical brain tissue and plasma samples from patients with refractory TLE, but miR-935 not. Plasma miRNA-129-2-3p has great potential as a non-invasive biomarker for early detection and clinical evaluation of refractory TLE.

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