Possible sexually dimorphic role of miRNA and other sncRNA in ASD brain.
Possible sexually dimorphic role of miRNA and other sncRNA in ASD brain.
复制标题
DOI：
10.1186/s13229-017-0117-0
复制
发表时间：
2017
期刊：
影响因子：
6.2
通讯作者：
Stamova B
中科院分区：
文献类型：
--
作者：
Schumann CM;Sharp FR;Ander BP;Stamova B
自闭症谱系障碍（ASD）在大脑结构、遗传和行为方面具有性别二态性。在脑组织的研究中，人口的年龄显然是解释研究结果的一个因素，但很少考虑性别。为了开始解决这个问题，我们扩展了我们以前发表的微阵列分析，以检查表达的小非编码RNA（sncRNA），包括microRNA（miRNA），在ASD和在控制颞叶皮层的男性和女性。确定了预测的miRNA靶点以及它们过度填充的途径。在考虑年龄后，ASD sncRNA表达的性别二态性在颞叶皮层和区分区域的模式中仍然存在。在性二态性miRNA中，有促进少突胶质细胞分化的miR-219和miR-338，涉及神经元分化的miR-125，以及涉及焦虑的miR-488。假定的miRNA靶点在两种性别的免疫和神经系统途径中显著过量，与先前的mRNA研究一致。即使是常见的途径，特定的目标mRNA往往是性别二态性。例如，男性和女性的靶基因都显著地填充了轴突指导信号通路，但不到三分之一的靶基因是两性共有的。我们在sncRNA水平上的性二态性的发现强调了在解释ASD大脑的分子发现时，除了年龄之外，还要考虑性别的重要性。本文的在线版本（doi：10.1186/s13229-017-0117-0）包含补充材料，可供授权用户使用。
Autism spectrum disorder (ASD) is sexually dimorphic in brain structure, genetics, and behaviors. In studies of brain tissue, the age of the population is clearly a factor in interpreting study outcome, yet sex is rarely considered. To begin to address this issue, we extend our previously published microarray analyses to examine expression of small noncoding RNAs (sncRNAs), including microRNAs (miRNAs), in ASD and in the control temporal cortex in males and females. Predicted miRNA targets were identified as well as the pathways they overpopulate. After considering age, sexual dimorphism in ASD sncRNA expression persists in the temporal cortex and in the patterning that distinguishes regions. Among the sexually dimorphic miRNAs are miR-219 and miR-338, which promote oligodendrocyte differentiation, miR-125, implicated in neuronal differentiation, and miR-488, implicated in anxiety. Putative miRNA targets are significantly over-represented in immune and nervous system pathways in both sexes, consistent with previous mRNA studies. Even for common pathways, the specific target mRNAs are often sexually dimorphic. For example, both male and female target genes significantly populate the Axonal Guidance Signaling pathway, yet less than a third of the targets are common to both sexes. Our findings of sexual dimorphism in sncRNA levels underscore the importance of considering sex, in addition to age, when interpreting molecular findings on ASD brain. The online version of this article (doi:10.1186/s13229-017-0117-0) contains supplementary material, which is available to authorized users.