Dual-center, dual-platform microRNA profiling identifies potential plasma biomarkers of adult temporal lobe epilepsy

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Title: Dual-center, dual-platform microRNA profiling identifies potential plasma biomarkers of adult temporal lobe epilepsy
Authors: Raoof, RanaBauer, SebastianEl-Naggar, HanyMooney, Catherineet al.
Permanent link: http://hdl.handle.net/10197/10619
Date: 2-Nov-2018
Online since: 2019-05-22T13:42:19Z
Abstract: Background: There are no blood-based molecular biomarkers of temporal lobe epilepsy (TLE) to support clinical diagnosis. MicroRNAs are short noncoding RNAs with strong biomarker potential due to their cell-specific expression, mechanistic links to brain excitability, and stable detection in biofluids. Altered levels of circulating microRNAs have been reported in human epilepsy, but most studies collected samples from one clinical site, used a single profiling platform or conducted minimal validation. Method: Using a case-control design, we collected plasma samples from video-electroencephalogram-monitored adult TLE patients at epilepsy specialist centers in two countries, performed genome-wide PCR-based and RNA sequencing during the discovery phase and validated findings in a large (>250) cohort of samples that included patients with psychogenic non-epileptic seizures (PNES). Findings: After profiling and validation, we identified miR-27a-3p, miR-328-3p and miR-654-3p with biomarker potential. Plasma levels of these microRNAs were also changed in a mouse model of TLE but were not different to healthy controls in PNES patients. We determined copy number of the three microRNAs in plasma and demonstrate their rapid detection using an electrochemical RNA microfluidic disk as a prototype point-of-care device. Analysis of the microRNAs within the exosome-enriched fraction provided high diagnostic accuracy while Argonaute-bound miR-328-3p selectively increased in patient samples after seizures. In situ hybridization localized miR-27a-3p and miR-328-3p within neurons in human brain and bioinformatics predicted targets linked to growth factor signaling and apoptosis. Interpretation: This study demonstrates the biomarker potential of circulating microRNAs for epilepsy diagnosis and mechanistic links to underlying pathomechanisms.
Funding Details: European Commission - European Regional Development Fund
European Commission - Seventh Framework Programme (FP7)
Science Foundation Ireland
metadata.dc.description.othersponsorship: FutureNeuro industry partners
Citizens United for Research in Epilepsy
Detlev-Wrobel-Fonds for Epilepsy Research Frankfurt
Iraqi Ministry of Higher Education and Scientific Research
Type of material: Journal Article
Publisher: Elsevier
Journal: EBioMedicine
Volume: 38
End page: 127
Copyright (published version): 2018 the Authors
Keywords: BiofluidsDissociative seizuresNoncoding RNASerumStatus epilepticusTemporal lobe epilepsy
DOI: 10.1016/j.ebiom.2018.10.068
Language: en
Status of Item: Peer reviewed
Appears in Collections:Computer Science Research Collection

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