Dysregulation of miRNA 181b in the temporal cortex in schizophrenia
Dysregulation of miRNA 181b in the temporal cortex in schizophrenia
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DOI：
10.1093/hmg/ddn005
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发表时间：
2008-04-15
影响因子：
3.5
通讯作者：
Cairns, Murray J.
中科院分区：
文献类型：
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作者：
Beveridge, Natalie J.;Tooney, Paul A.;Cairns, Murray J.
对来自上级颞回的死后皮质灰质中的总体microRNA（miRNA）表达的分析显示，精神分裂症中miR-181 b表达显著上调。这一发现得到了21对精神分裂症和非精神病对照组中miRNA表达的定量实时RT-PCR分析的支持。这一发现的意义是重大的，因为预计这种miRNA可以调节许多对精神分裂症的发展具有潜在意义的靶基因。它们包括钙传感器基因visin-like 1（VSNL 1）和离子型AMPA谷氨酸受体亚基（GRIA 2），发现它们在精神分裂症组的相同皮质组织中下调。这两个基因在miR-181 b转染的细胞中也被抑制，并通过报告基因测定显示含有功能性miR-181 b miRNA识别元件。这项研究表明，miRNA水平的改变可能是精神分裂症患者皮质基因表达失调的一个重要因素。
Analysis of global microRNA (miRNA) expression in postmortem cortical grey matter from the superior temporal gyrus, revealed significant up-regulation of miR-181b expression in schizophrenia. This finding was supported by quantitative real-time RT-PCR analysis of miRNA expression in a cohort of 21 matched pairs of schizophrenia and non-psychiatric controls. The implications of this finding are substantial, as this miRNA is predicted to regulate many target genes with potential significance to the development of schizophrenia. They include the calcium sensor gene visinin-like 1 (VSNL1) and the ionotropic AMPA glutamate receptor subunit (GRIA2), which were found to be down-regulated in the same cortical tissue from the schizophrenia group. Both of these genes were also suppressed in miR-181b transfected cells and shown to contain functional miR-181b miRNA recognition elements by reporter gene assay. This study suggests altered miRNA levels could be a significant factor in the dysregulation of cortical gene expression in schizophrenia.