Circulating MicroRNAs from Serum Exosomes May Serve as a Putative Biomarker in the Diagnosis and Treatment of Patients with Focal Cortical Dysplasia.

Abstract

Focal cortical dysplasia (FCD) is a congenital malformation of cortical development where the cortical neurons located in the brain area fail to migrate in the proper formation. Epilepsy, particularly medically refractory epilepsy, is the most common clinical presentation for all types of FCD. This study aimed to explore the expression change of circulating miRNAs in patients with FCD from serum exosomes. A total of nine patients with FCD and four healthy volunteers were enrolled in this study. The serum exosomes were isolated from the peripheral blood of the subjects. Transmission electron microscopy (TEM) was used to identify the exosomes. Both exosomal markers and neuronal markers were detected by Western blotting analysis to prove that we could obtain central nervous system-derived exosomes from the circulation. The expression profiles of circulating exosomal miRNAs were assessed using next-generation sequencing analysis (NGS). We obtained a total of 107 miRNAs with dominant fold change (>2-fold) from both the annotated 5p-arm and 3p-arm of 2780 mature miRNAs. Based on the integrated platform of HMDD v3.2, miRway DB and DIANA-miRPath v3.0 online tools, and confirmed by MiRBase analysis, four potentially predicted miRNAs from serum exosomes in patients with FCD were identified, including miR194-2-5p, miR15a-5p, miR-132-3p, and miR-145-5p. All four miRNAs presented upregulated expression in patients with FCD compared with controls. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and pathway category of four target miRNAs, we found eight possible signaling pathways that may be related to FCD. Among them, we suggest that the mTOR signaling pathway, PI3K-Akt signaling pathway, p53 signaling pathway, and cell cycle regulation and TGF-beta signaling pathway are high-risk pathways that play a crucial role in the pathogenesis of FCD and refractory epilepsy. Our results suggest that the circulating miRNAs from exosomes may provide a potential biomarker for diagnostic, prognostic, and therapeutic adjuncts in patients with FCD and refractory epilepsy.

• Authors: Shang-Der Chen, Hsiu-Yung Pan, Jyun-Bin Huang, Xuan-Ping Liu, Jie-Hau Li, Chen-Jui Ho, Meng-Han Tsai, Jenq-Lin Yang, Shu-Fang Chen, Nai-Ching Chen, Yao-Chung Chuang
• Journal: Cells (Cells) Vol. 9 Issue 8 (08 10 2020) ISSN: 2073-4409 [Electronic] Switzerland
• PMID: 32785072 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Circulating MicroRNA

Topics

• Adolescent
• Adult
• Biomarkers (blood)
• Blotting, Western
• Case-Control Studies
• Circulating MicroRNA (genetics, metabolism)
• Epilepsy (blood, diagnosis, epidemiology, therapy)
• Exosomes (metabolism)
• Female
• High-Throughput Nucleotide Sequencing
• Humans
• Male
• Malformations of Cortical Development, Group I (blood, diagnosis, epidemiology, therapy)
• Microscopy, Electron, Transmission
• Middle Aged
• Prognosis
• Taiwan (epidemiology)
• Up-Regulation
• Young Adult