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Article

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

by
Shang-Der Chen
1,2,3,†,
Hsiu-Yung Pan
4,†,
Jyun-Bin Huang
4,
Xuan-Ping Liu
2,
Jie-Hau Li
2,
Chen-Jui Ho
1,
Meng-Han Tsai
1,3,
Jenq-Lin Yang
2,
Shu-Fang Chen
1,
Nai-Ching Chen
1 and
Yao-Chung Chuang
1,2,3,5,6,*
1
Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
2
Institute for Translation Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
3
College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
4
Department of Emergency Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan
5
Department of Neurology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
6
Department of Biological Science, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2020, 9(8), 1867; https://doi.org/10.3390/cells9081867
Submission received: 2 July 2020 / Revised: 3 August 2020 / Accepted: 8 August 2020 / Published: 10 August 2020
(This article belongs to the Section Intracellular and Plasma Membranes)
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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.
Keywords: focal cortical dysplasia; microRNA; exosomes; biomarkers; circulation focal cortical dysplasia; microRNA; exosomes; biomarkers; circulation

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MDPI and ACS Style

Chen, S.-D.; Pan, H.-Y.; Huang, J.-B.; Liu, X.-P.; Li, J.-H.; Ho, C.-J.; Tsai, M.-H.; Yang, J.-L.; Chen, S.-F.; Chen, N.-C.; et al. Circulating MicroRNAs from Serum Exosomes May Serve as a Putative Biomarker in the Diagnosis and Treatment of Patients with Focal Cortical Dysplasia. Cells 2020, 9, 1867. https://doi.org/10.3390/cells9081867

AMA Style

Chen S-D, Pan H-Y, Huang J-B, Liu X-P, Li J-H, Ho C-J, Tsai M-H, Yang J-L, Chen S-F, Chen N-C, et al. Circulating MicroRNAs from Serum Exosomes May Serve as a Putative Biomarker in the Diagnosis and Treatment of Patients with Focal Cortical Dysplasia. Cells. 2020; 9(8):1867. https://doi.org/10.3390/cells9081867

Chicago/Turabian Style

Chen, Shang-Der, 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, and et al. 2020. "Circulating MicroRNAs from Serum Exosomes May Serve as a Putative Biomarker in the Diagnosis and Treatment of Patients with Focal Cortical Dysplasia" Cells 9, no. 8: 1867. https://doi.org/10.3390/cells9081867

APA Style

Chen, S.-D., Pan, H.-Y., Huang, J.-B., Liu, X.-P., Li, J.-H., Ho, C.-J., Tsai, M.-H., Yang, J.-L., Chen, S.-F., Chen, N.-C., & Chuang, Y.-C. (2020). Circulating MicroRNAs from Serum Exosomes May Serve as a Putative Biomarker in the Diagnosis and Treatment of Patients with Focal Cortical Dysplasia. Cells, 9(8), 1867. https://doi.org/10.3390/cells9081867

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