Schizophrenia Research Institute, Sydney, NSW, Australia.
Mol Psychiatry. 2010 Dec;15(12):1176-89. doi: 10.1038/mp.2009.84. Epub 2009 Sep 1.
MicroRNA expression profiling and quantitative reverse transcription-PCR analysis of the superior temporal gyrus and the dorsolateral prefrontal cortex revealed a significant schizophrenia-associated increase in global microRNA expression. This change was associated with an elevation of primary microRNA processing and corresponded with an increase in the microprocessor component DGCR8. The biological implications for this extensive increase in gene silencing are profound, and were exemplified by members of the miR-15 family and other related microRNA, which were significantly upregulated in both brain regions. This functionally convergent influence is overrepresented in pathways involved in synaptic plasticity and includes many genes and pathways associated with schizophrenia, some of which were substantiated in vitro by reporter gene assay. Given the magnitude of microRNA changes and their wide sphere of influence, this phenomenon could represent an important dimension in the pathogenesis of schizophrenia.
对优势颞叶和背外侧前额叶皮层的 microRNA 表达谱和定量逆转录-PCR 分析显示，全局 microRNA 表达显著增加与精神分裂症相关。这种变化与初级 microRNA 加工的升高有关，并且与 microprocessor 成分 DGCR8 的增加相对应。这种广泛的基因沉默增加的生物学意义是深远的，以 miR-15 家族和其他相关 microRNA 的成员为例，它们在两个脑区均显著上调。这种功能上的趋同影响在涉及突触可塑性的途径中过度表达，包括许多与精神分裂症相关的基因和途径，其中一些在体外通过报告基因检测得到证实。鉴于 microRNA 变化的幅度及其广泛的影响范围，这种现象可能代表精神分裂症发病机制中的一个重要方面。
