Identification of a miRNAs signature associated with exposure to stress early in life and enhanced vulnerability for schizophrenia: New insights for the key role of miR-125b-1-3p in neurodevelopmental processes
Identification of a miRNAs signature associated with exposure to stress early in life and enhanced vulnerability for schizophrenia: New insights for the key role of miR-125b-1-3p in neurodevelopmental processes
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DOI：
10.1016/j.schres.2018.07.030
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发表时间：
2019-03-01
影响因子：
4.5
通讯作者：
Cattaneo, Annamaria
中科院分区：
文献类型：
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作者：
Cattane, Nadia;Mora, Cristina;Cattaneo, Annamaria
流行病学和临床研究为遗传和环境因素（例如生命早期的压力经历）在精神分裂症（SZ）发病机制中的作用提供了证据，并且 microRNA（miRNA）被认为在环境与我们的基因组之间的相互作用中发挥着关键作用。在这项研究中，我们对不同样本（暴露于童年创伤的成年受试者的血液、暴露于产前压力的大鼠的大脑（海马）和人类的大脑）进行了 miRNOme 分析。海马祖细胞用皮质醇处理），我们在所有三个数据集中将 miR-125b-1-3p 鉴定为下调的 miRNA。有趣的是，在遭受童年创伤的 SZ 患者中也观察到显着的下调。为了研究 miR-125b-1-3p 靶向并参与应激影响的生物系统，我们将预测和验证的 miR-125b-13p 靶基因调节的生物途径列表与体外模型中受皮质醇显着调节的生物系统结合起来。我们发现 CXCR4 信号传导、G-α 信号传导和 P2Y 纯基因受体信号传导通路作为常见通路，它们都参与神经发育过程。我们的数据是通过组合不同组织和物种的 miRNA 数据集获得的，将 miR125b-1-3p 确定为与生命早期压力的长期影响以及发育中的 SZ 的脆弱性增强相关的关键标志物。这种 miRNA 生物标志物的鉴定可以帮助早期发现 SZ 易感受试者，并为制定预防性治疗策略提供基础。 (C) 2018 年由 Elsevier B.V. 出版
Epidemiological and clinical studies have provided evidence for a role of both genetic and environmental factors, such as stressful experiences early in life, in the pathogenesis of Schizophrenia (SZ) and microRNAs (miRNAs) have been suggested to play a key role in the interplay between the environment and our genome.In this study, we conducted a miRNOme analysis in different samples (blood of adult subjects exposed to childhood trauma, brain (hippocampus) of rats exposed to prenatal stress and human hippocampal progenitor cells treated with cortisol) and we identified miR-125b-1-3p as a down-regulated miRNA in all the three datasets. Interestingly, a significant down-regulation was observed also in SZ patients exposed to childhood trauma. To investigate the biological systems targeted by miR-125b-1-3p and also involved in the effects of stress, we combined the list of biological pathways modulated by predicted and validated target genes of miR-125b-13p, with the biological systems significantly regulated by cortisol in the in vitro model. We found, as common pathways, the CXCR4 signaling, the G-alpha signaling, and the P2Y Purigenic Receptor Signaling Pathway, which are all involved in neurodevelopmental processes.Our data, obtained from the combining of miRNAs datasets across different tissues and species, identified miR125b-1-3p as a key marker associated with the long-term effects of stress early in life and also with the enhanced vulnerability of developing SZ. The identification of such a miRNA biomarker could allow the early detection of vulnerable subjects for SZ and could provide the basis for the development of preventive therapeutic strategies. (C) 2018 Published by Elsevier B.V.