Beveridge Natalie J, Tooney Paul A, Carroll Adam P, Gardiner Erin, Bowden Nikola, Scott Rodney J, Tran Nham, Dedova Irina, Cairns Murray J
Schizophrenia Research Institute, Sydney, NSW 2006, Australia.
Hum Mol Genet. 2008 Apr 15;17(8):1156-68. doi: 10.1093/hmg/ddn005. Epub 2008 Jan 9.
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.
对来自颞上回的死后皮质灰质中的全球微小RNA(miRNA)表达进行分析,结果显示精神分裂症患者中miR-181b表达显著上调。对21对匹配的精神分裂症患者和非精神疾病对照队列中的miRNA表达进行定量实时RT-PCR分析,支持了这一发现。这一发现的意义重大,因为预计这种miRNA可调节许多对精神分裂症发展具有潜在重要性的靶基因。它们包括钙传感器基因类视黄醛蛋白1(VSNL1)和离子型AMPA谷氨酸受体亚基(GRIA2),在精神分裂症组的同一皮质组织中发现它们表达下调。在转染了miR-181b的细胞中,这两个基因也受到抑制,并且通过报告基因测定显示它们含有功能性miR-181b 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皮质基因表达失调的一个重要因素。