Altered expression of microRNA-223 in the plasma of patients with first-episode schizophrenia and its possible relation to neuronal migration-related genes
Altered expression of microRNA-223 in the plasma of patients with first-episode schizophrenia and its possible relation to neuronal migration-related genes
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DOI：
10.1038/s41398-019-0609-0
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发表时间：
2019-11
影响因子：
6.8
通讯作者：
Zhilei Zhao;S. Jinde;S. Koike;M. Tada;Yoshihiro Satomura;Akane Yoshikawa;Y. Nishimura;R. Takizawa;Akihide Kinoshita;Eisuke Sakakibara;Hanako Sakurada;Mika Yamagishi;Fumichika Nishimura;Aya Inai;Masaki Nishioka;Yosuke Eriguchi;T. Araki;A. Takaya;Chiemi Kan;M. Umeda;A. Shimazu;H. Hashimoto;M. Bundo;K. Iwamoto;Chihiro Kakiuchi;K. Kasai
中科院分区：
文献类型：
--
作者：
Zhilei Zhao;S. Jinde;S. Koike;M. Tada;Yoshihiro Satomura;Akane Yoshikawa;Y. Nishimura;R. Takizawa;Akihide Kinoshita;Eisuke Sakakibara;Hanako Sakurada;Mika Yamagishi;Fumichika Nishimura;Aya Inai;Masaki Nishioka;Yosuke Eriguchi;T. Araki;A. Takaya;Chiemi Kan;M. Umeda;A. Shimazu;H. Hashimoto;M. Bundo;K. Iwamoto;Chihiro Kakiuchi;K. Kasai
最近的研究表明，microRNAs（miRNAs）通过调节基因表达，在神经发育中发挥调节作用。在包括精神分裂症在内的各种精神疾病中已经报道了改变的miRNA表达。然而，在精神分裂症的初始阶段发生的miRNA表达谱的变化还没有得到充分的研究。为了探索可能与精神分裂症发病相关的miRNA表达谱的整体变化，我们首先使用微阵列分析对17名首发精神分裂症患者和17名健康对照者的血浆中的miRNA表达进行了分析。在显示出稳健变化的miRNAs中，has-miR-223- 3 p（miR-223）的表达升高通过定量逆转录聚合酶链反应（qRT-PCR）进行验证，使用另一个独立的样本集21名精神分裂症患者和21名对照。为了确定miR-223的假定靶点，我们在具有稳定miR-223过表达的神经元分化的SK-N-SH细胞中进行了全基因组基因表达分析和计算机模拟分析。我们发现，与细胞骨架或细胞迁移相关的四个基因的mRNA表达水平在miR-223过表达的细胞中显著下调，可能是由于与miR-223的相互作用。计算机模拟分析表明这四个基因中存在miR-223靶位点。最后，荧光素酶测定证实miR-223与所有四个基因的3′非翻译区（UTR）直接相互作用。我们的研究结果揭示了在精神分裂症的第一次发作和后期，血浆中的miR-223的增加，这可能会影响miR-223靶向的细胞迁移相关基因的表达。
Recent studies have shown that microRNAs (miRNAs) play a role as regulators of neurodevelopment by modulating gene expression. Altered miRNA expression has been reported in various psychiatric disorders, including schizophrenia. However, the changes in the miRNA expression profile that occur during the initial stage of schizophrenia have not been fully investigated. To explore the global alterations in miRNA expression profiles that may be associated with the onset of schizophrenia, we first profiled miRNA expression in plasma from 17 patients with first-episode schizophrenia and 17 healthy controls using microarray analysis. Among the miRNAs that showed robust changes, the elevated expression of has-miR-223-3p (miR-223) was validated via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using another independent sample set of 21 schizophrenia patients and 21 controls. To identify the putative targets of miR-223, we conducted a genome-wide gene expression analysis in neuronally differentiated SK-N-SH cells with stable miR-223 overexpression and an in silico analysis. We found that the mRNA expression levels of four genes related to the cytoskeleton or cell migration were significantly downregulated in miR-223-overexpressing cells, possibly due to interactions with miR-223. The in silico analysis suggested the presence of miR-223 target sites in these four genes. Lastly, a luciferase assay confirmed that miR-223 directly interacted with the 3′ untranslated regions (UTRs) of all four genes. Our results reveal an increase in miR-223 in plasma during both the first episode and the later stage of schizophrenia, which may affect the expression of cell migration-related genes targeted by miR-223.