Circulating exosomal microRNAs in bipolar disorder
Circulating exosomal microRNAs in bipolar disorder
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DOI：
10.1016/j.jad.2019.10.038
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发表时间：
2020-02-01
影响因子：
6.6
通讯作者：
Ozerdem, Aysegul
中科院分区：
文献类型：
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作者：
Ceylan, Deniz;Tufekci, Kemal Ugur;Ozerdem, Aysegul
前言：新的证据表明miRNAs在双相情感障碍(BD)的发病机制中起着中心作用。Exosome是一种膜结合的囊泡，可以作为包括microRNAs在内的各种分子的“生物货运载体”。方法：从BD患者(n=69，抑郁15例，躁狂27例，心境良好27例)和正常对照(n=41)的血浆标本中提取外切体。提取外切体总RNA，用定量聚合酶链式反应检测miRNAs水平。结果：13个miRNAs在BD患者和健康人之间存在显著差异，其中miR-484、-652-3p、-142-3p表达显著下调，miR-185-5p表达显著上调。不同的BD状态之间没有明显的变化。通过对4条miRNAs异常表达的KEEG分析，揭示了PI3K/Akt信号转导、脂肪酸生物合成/代谢、细胞外基质和黏附途径等多种靶向通路。结论：miRNAs表达异常可能通过多种生物学途径参与BD的发病机制，并强调外体miRNAs在BD生物标记物研究中的重要性。进一步的纵向研究可能会阐明外体miRNAs及其靶点在BD神经生物学中的作用。
Introduction: Emerging evidence suggests central roles of miRNAs in the pathogenesis of bipolar disorder (BD). Exosomes are membrane-bound vesicles acing as "biological cargo carriers" of various types of molecules including microRNAs. In this study, we aimed to investigate circulating exosomal microRNAs as potential diagnostic biomarkers for BD.Methods: The exosomes were precipitated from plasma samples of patients with BD (n = 69; 15 depressed, 27 manic, 27 euthymic) and healthy controls (n. = 41). Total RNA was extracted from the exosomes and the levels of miRNAs were assayed by qPCR. Dysregulated miRNAs were subjected to Kyoto Encyclopedia of Genes and Genomes" (KEGG) pathway analysis by DIANA-miRPath v3.0 to identify the predicted targets and the related pathways.Results: Thirteen miRNAs showed significant differences between patients with BD and healthy individuals; among these, MiR-484, -652-3p, -142-3p remained significantly downregulated and miR-185-5p remained significantly upregulated after accounting for multiple comparisons and adjustments for potential confounders. There were no significant alterations among different states of BD. The KEEG analysis of four dysregulated miRNAs highlighted several target pathways including PI3K/Akt signaling, fatty acid biosynthesis/metabolism, extracellular matrix and adhesion pathways.Conclusion: Our findings suggest that dysregulation of miRNAs might be involved in the underlying pathophysiology of BD through several biological pathways; and highlight the importance of the exosomal miRNAs for biomarker research in BD. Further longitudinal studies may clarify the roles of exosomal miRNAs and their targets in the neurobiology of BD.